Last data update: Dec 09, 2024. (Total: 48320 publications since 2009)
Records 1-30 (of 30 Records) |
Query Trace: Kuzmin I[original query] |
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2022 taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.
Kuhn JH , Adkins S , Alkhovsky SV , Avi-upanc T , Aylln MA , Bahl J , Balkema-Buschmann A , Ballinger MJ , Bandte M , Beer M , Bejerman N , Bergeron , Biedenkopf N , Bigarr L , Blair CD , Blasdell KR , Bradfute SB , Briese T , Brown PA , Bruggmann R , Buchholz UJ , Buchmeier MJ , Bukreyev A , Burt F , Bttner C , Calisher CH , Candresse T , Carson J , Casas I , Chandran K , Charrel RN , Chiaki Y , Crane A , Crane M , Dacheux L , B ED , delaTorre JC , deLamballerie X , deSouza WM , deSwart RL , Dheilly NM , DiPaola N , DiSerio F , Dietzgen RG , Digiaro M , Drexler JF , Duprex WP , Drrwald R , Easton AJ , Elbeaino T , Ergnay K , Feng G , Feuvrier C , Firth AE , Fooks AR , Formenty PBH , Freitas-Asta J , Gago-Zachert S , Garca ML , Garca-Sastre A , Garrison AR , Godwin SE , Gonzalez JJ , deBellocq JG , Griffiths A , Groschup MH , Gnther S , Hammond J , Hepojoki J , Hierweger MM , Hong S , Horie M , Horikawa H , Hughes HR , Hume AJ , Hyndman TH , Jing D , Jonson GB , Junglen S , Kadono F , Karlin DG , Klempa B , Klingstrm J , Koch MC , Kond H , Koonin EV , Krsov J , Krupovic M , Kubota K , Kuzmin IV , Laenen L , Lambert AJ , L J , Li JM , Lieffrig F , Lukashevich IS , Luo D , Maes P , Marklewitz M , Marshall SH , Marzano SL , McCauley JW , Mirazimi A , Mohr PG , Moody NJG , Morita Y , Morrison RN , Mhlberger E , Naidu R , Natsuaki T , Navarro JA , Neriya Y , Netesov SV , Neumann G , Nowotny N , Ochoa-Corona FM , Palacios G , Pallandre L , Palls V , Papa A , Paraskevopoulou S , Parrish CR , Pauvolid-Corra A , Pawska JT , Prez DR , Pfaff F , Plemper RK , Postler TS , Pozet F , Radoshitzky SR , Ramos-Gonzlez PL , Rehanek M , Resende RO , Reyes CA , Romanowski V , Rubbenstroth D , Rubino L , Rumbou A , Runstadler JA , Rupp M , Sabanadzovic S , Sasaya T , Schmidt-Posthaus H , Schwemmle M , Seuberlich T , Sharpe SR , Shi M , Sironi M , Smither S , Song JW , Spann KM , Spengler JR , Stenglein MD , Takada A , Tesh RB , Tkov J , Thornburg NJ , Tischler ND , Tomitaka Y , Tomonaga K , Tordo N , Tsunekawa K , Turina M , Tzanetakis IE , Vaira AM , vandenHoogen B , Vanmechelen B , Vasilakis N , Verbeek M , vonBargen S , Wada J , Wahl V , Walker PJ , Whitfield AE , Williams JV , Wolf YI , Yamasaki J , Yanagisawa H , Ye G , Zhang YZ , kland AL . Arch Virol 2022 167 (12) 2857-2906 In March 2022, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by two new families (bunyaviral Discoviridae and Tulasviridae), 41 new genera, and 98 new species. Three hundred forty-nine species were renamed and/or moved. The accidentally misspelled names of seven species were corrected. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV. |
2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.
Kuhn JH , Adkins S , Alioto D , Alkhovsky SV , Amarasinghe GK , Anthony SJ , Avšič-Županc T , Ayllón MA , Bahl J , Balkema-Buschmann A , Ballinger MJ , Bartonička T , Basler C , Bavari S , Beer M , Bente DA , Bergeron É , Bird BH , Blair C , Blasdell KR , Bradfute SB , Breyta R , Briese T , Brown PA , Buchholz UJ , Buchmeier MJ , Bukreyev A , Burt F , Buzkan N , Calisher CH , Cao M , Casas I , Chamberlain J , Chandran K , Charrel RN , Chen B , Chiumenti M , Choi IR , Clegg JCS , Crozier I , da Graça JV , Dal Bó E , Dávila AMR , de la Torre JC , de Lamballerie X , de Swart RL , Di Bello PL , Di Paola N , Di Serio F , Dietzgen RG , Digiaro M , Dolja VV , Dolnik O , Drebot MA , Drexler JF , Dürrwald R , Dufkova L , Dundon WG , Duprex WP , Dye JM , Easton AJ , Ebihara H , Elbeaino T , Ergünay K , Fernandes J , Fooks AR , Formenty PBH , Forth LF , Fouchier RAM , Freitas-Astúa J , Gago-Zachert S , Gāo GF , García ML , García-Sastre A , Garrison AR , Gbakima A , Goldstein T , Gonzalez JJ , Griffiths A , Groschup MH , Günther S , Guterres A , Hall RA , Hammond J , Hassan M , Hepojoki J , Hepojoki S , Hetzel U , Hewson R , Hoffmann B , Hongo S , Höper D , Horie M , Hughes HR , Hyndman TH , Jambai A , Jardim R , Jiāng D , Jin Q , Jonson GB , Junglen S , Karadağ S , Keller KE , Klempa B , Klingström J , Kobinger G , Kondō H , Koonin EV , Krupovic M , Kurath G , Kuzmin IV , Laenen L , Lamb RA , Lambert AJ , Langevin SL , Lee B , Lemos ERS , Leroy EM , Li D , Lǐ J , Liang M , Liú W , Liú Y , Lukashevich IS , Maes P , Marciel de Souza W , Marklewitz M , Marshall SH , Martelli GP , Martin RR , Marzano SL , Massart S , McCauley JW , Mielke-Ehret N , Minafra A , Minutolo M , Mirazimi A , Mühlbach HP , Mühlberger E , Naidu R , Natsuaki T , Navarro B , Navarro JA , Netesov SV , Neumann G , Nowotny N , Nunes MRT , Nylund A , Økland AL , Oliveira RC , Palacios G , Pallas V , Pályi B , Papa A , Parrish CR , Pauvolid-Corrêa A , Pawęska JT , Payne S , Pérez DR , Pfaff F , Radoshitzky SR , Rahman AU , Ramos-González PL , Resende RO , Reyes CA , Rima BK , Romanowski V , Robles Luna G , Rota P , Rubbenstroth D , Runstadler JA , Ruzek D , Sabanadzovic S , Salát J , Sall AA , Salvato MS , Sarpkaya K , Sasaya T , Schwemmle M , Shabbir MZ , Shí X , Shí Z , Shirako Y , Simmonds P , Širmarová J , Sironi M , Smither S , Smura T , Song JW , Spann KM , Spengler JR , Stenglein MD , Stone DM , Straková P , Takada A , Tesh RB , Thornburg NJ , Tomonaga K , Tordo N , Towner JS , Turina M , Tzanetakis I , Ulrich RG , Vaira AM , van den Hoogen B , Varsani A , Vasilakis N , Verbeek M , Wahl V , Walker PJ , Wang H , Wang J , Wang X , Wang LF , Wèi T , Wells H , Whitfield AE , Williams JV , Wolf YI , Wú Z , Yang X , Yáng X , Yu X , Yutin N , Zerbini FM , Zhang T , Zhang YZ , Zhou G , Zhou X . Arch Virol 2020 165 (12) 3023-3072 In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV. |
Taxonomy of the order Mononegavirales: update 2019.
Amarasinghe GK , Ayllon MA , Bao Y , Basler CF , Bavari S , Blasdell KR , Briese T , Brown PA , Bukreyev A , Balkema-Buschmann A , Buchholz UJ , Chabi-Jesus C , Chandran K , Chiapponi C , Crozier I , de Swart RL , Dietzgen RG , Dolnik O , Drexler JF , Durrwald R , Dundon WG , Duprex WP , Dye JM , Easton AJ , Fooks AR , Formenty PBH , Fouchier RAM , Freitas-Astua J , Griffiths A , Hewson R , Horie M , Hyndman TH , Jiang D , Kitajima EW , Kobinger GP , Kondo H , Kurath G , Kuzmin IV , Lamb RA , Lavazza A , Lee B , Lelli D , Leroy EM , Li J , Maes P , Marzano SL , Moreno A , Muhlberger E , Netesov SV , Nowotny N , Nylund A , Okland AL , Palacios G , Palyi B , Paweska JT , Payne SL , Prosperi A , Ramos-Gonzalez PL , Rima BK , Rota P , Rubbenstroth D , Shi M , Simmonds P , Smither SJ , Sozzi E , Spann K , Stenglein MD , Stone DM , Takada A , Tesh RB , Tomonaga K , Tordo N , Towner JS , van den Hoogen B , Vasilakis N , Wahl V , Walker PJ , Wang LF , Whitfield AE , Williams JV , Zerbini FM , Zhang T , Zhang YZ , Kuhn JH . Arch Virol 2019 164 (7) 1967-1980 In February 2019, following the annual taxon ratification vote, the order Mononegavirales was amended by the addition of four new subfamilies and 12 new genera and the creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV). |
Taxonomy of the order Mononegavirales: second update 2018
Maes P , Amarasinghe GK , Ayllon MA , Basler CF , Bavari S , Blasdell KR , Briese T , Brown PA , Bukreyev A , Balkema-Buschmann A , Buchholz UJ , Chandran K , Crozier I , de Swart RL , Dietzgen RG , Dolnik O , Domier LL , Drexler JF , Durrwald R , Dundon WG , Duprex WP , Dye JM , Easton AJ , Fooks AR , Formenty PBH , Fouchier RAM , Freitas-Astua J , Ghedin E , Griffiths A , Hewson R , Horie M , Hurwitz JL , Hyndman TH , Jiang D , Kobinger GP , Kondo H , Kurath G , Kuzmin IV , Lamb RA , Lee B , Leroy EM , Li J , Marzano SL , Muhlberger E , Netesov SV , Nowotny N , Palacios G , Palyi B , Paweska JT , Payne SL , Rima BK , Rota P , Rubbenstroth D , Simmonds P , Smither SJ , Song Q , Song T , Spann K , Stenglein MD , Stone DM , Takada A , Tesh RB , Tomonaga K , Tordo N , Towner JS , van den Hoogen B , Vasilakis N , Wahl V , Walker PJ , Wang D , Wang LF , Whitfield AE , Williams JV , Ye G , Zerbini FM , Zhang YZ , Kuhn JH . Arch Virol 2019 164 (4) 1233-1244 In October 2018, the order Mononegavirales was amended by the establishment of three new families and three new genera, abolishment of two genera, and creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV). |
In Vivo Efficacy of a Cocktail of Human Monoclonal Antibodies (CL184) Against Diverse North American Bat Rabies Virus Variants
Franka R , Carson WC , Ellison JA , Taylor ST , Smith TG , Kuzmina NA , Kuzmin IV , Marissen WE , Rupprecht CE . Trop Med Infect Dis 2017 2 (3) Following rabies virus (RABV) exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG) are essential components of modern post-exposure prophylaxis (PEP). Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG is much less available. The prohibitive cost of polyclonal serum RIG products has prompted a search for alternatives and design of anti-RABV monoclonal antibodies (MAbs) that can be manufactured on a large scale with a consistent potency and lower production costs. Robust in vitro neutralization activity has been demonstrated for the CL184 MAb cocktail, a 1:1 protein mixture of two human anti-RABV MAbs (CR57/CR4098), against a large panel of RABV isolates. In this study, we used a hamster model to evaluate the efficacy of experimental PEP against a lethal challenge. Various doses of CL184 and commercial rabies vaccine were assessed for the ability to protect against lethal infection with representatives of four distinct bat RABV lineages of public health relevance: silver-haired bat (Ln RABV); western canyon bat (Ph RABV); big brown bat (Ef-w1 RABV) and Mexican free-tailed bat RABV (Tb RABV). 42⁻100% of animals survived bat RABV infection when CL184 (in combination with the vaccine) was administered. A dose-response relationship was observed with decreasing doses of CL184 resulting in increasing mortality. Importantly, CL184 was highly effective in neutralizing and clearing Ph RABV in vivo, even though CR4098 does not neutralize this virus in vitro. By comparison, 19⁻95% survivorship was observed if human RIG (20 IU/kg) and vaccine were used following challenge with different bat viruses. Based on our results, CL184 represents an efficacious alternative for RIG. Both large-scale and lower cost production could ensure better availability and affordability of this critical life-saving biologic in rabies enzootic countries and as such, significantly contribute to the reduction of human rabies deaths globally. |
Prevalence, diversity, and host associations of Bartonella strains in bats from Georgia (Caucasus).
Urushadze L , Bai Y , Osikowicz L , McKee C , Sidamonidze K , Putkaradze D , Imnadze P , Kandaurov A , Kuzmin I , Kosoy M . PLoS Negl Trop Dis 2017 11 (4) e0005428 Bartonella infections were investigated in seven species of bats from four regions of the Republic of Georgia. Of the 236 bats that were captured, 212 (90%) specimens were tested for Bartonella infection. Colonies identified as Bartonella were isolated from 105 (49.5%) of 212 bats Phylogenetic analysis based on sequence variation of the gltA gene differentiated 22 unique Bartonella genogroups. Genetic distances between these diverse genogroups were at the level of those observed between different Bartonella species described previously. Twenty-one reference strains from 19 representative genogroups were characterized using four additional genetic markers. Host specificity to bat genera or families was reported for several Bartonella genogroups. Some Bartonella genotypes found in bats clustered with those identified in dogs from Thailand and humans from Poland. |
Molecular Survey of Bacterial Zoonotic Agents in Bats from the Country of Georgia (Caucasus).
Bai Y , Urushadze L , Osikowicz L , McKee C , Kuzmin I , Kandaurov A , Babuadze G , Natradze I , Imnadze P , Kosoy M . PLoS One 2017 12 (1) e0171175 Bats are important reservoirs for many zoonotic pathogens. However, no surveys of bacterial pathogens in bats have been performed in the Caucasus region. To understand the occurrence and distribution of bacterial infections in these mammals, 218 bats belonging to eight species collected from four regions of Georgia were examined for Bartonella, Brucella, Leptospira, and Yersinia using molecular approaches. Bartonella DNA was detected in 77 (35%) bats from all eight species and was distributed in all four regions. The prevalence ranged 6-50% per bat species. The Bartonella DNA represented 25 unique genetic variants that clustered into 21 lineages. Brucella DNA was detected in two Miniopterus schreibersii bats and in two Myotis blythii bats, all of which were from Imereti (west-central region). Leptospira DNA was detected in 25 (13%) bats that included four M. schreibersii bats and 21 M. blythii bats collected from two regions. The Leptospira sequences represented five genetic variants with one of them being closely related to the zoonotic pathogen L. interrogans (98.6% genetic identity). No Yersinia DNA was detected in the bats. Mixed infections were observed in several cases. One M. blythii bat and one M. schreibersii bat were co-infected with Bartonella, Brucella, and Leptospira; one M. blythii bat and one M. schreibersii bat were co-infected with Bartonella and Brucella; 15 M. blythii bats and three M. schreibersii bats were co-infected with Bartonella and Leptospira. Our results suggest that bats in Georgia are exposed to multiple bacterial infections. Further studies are needed to evaluate pathogenicity of these agents to bats and their zoonotic potential. |
Surveillance of bat coronaviruses in Kenya identifies relatives of human coronaviruses NL63 and 229E and their recombination history
Tao Y , Shi M , Chommanard C , Queen K , Zhang J , Markotter W , Kuzmin IV , Holmes EC , Tong S . J Virol 2017 91 (5) Bats harbor a large diversity of coronaviruses (CoVs), several of which are related to zoonotic pathogens that cause severe disease in humans. Our screening of bat samples collected in Kenya during 2007-2010 not only detected RNA from several novel CoVs but, more significantly, identified sequences that were closely related to human CoVs NL63 and 229E, suggesting that these two human viruses originate from bats. We also demonstrated that human CoV NL63 is a recombinant between NL63-like viruses circulating in Triaenops bats and 229E-like viruses circulating in Hipposideros bats, with the break-point located near 5' and 3' end of the spike (S) protein gene. In addition, two further inter-species recombination events involving the S gene were identified, suggesting that this region may represent a recombination "hotspot" in CoV genomes. Finally, using a combination of phylogenetic and distance-based approaches we showed that genetic diversity of bat CoVs is primarily structured by host species and subsequently by geographic distances. IMPORTANCE: Understanding the driving forces of cross-species virus transmission is central to understanding the nature of disease emergence. Previous studies have demonstrated that bats are the ultimate reservoir hosts for a number of coronaviruses (CoVs) including ancestors of SARS-CoV, MERS-CoV, and HCoV-229E. However, the evolutionary pathways of bat CoVs remain elusive. We provide evidence for natural recombination between distantly-related African bat coronaviruses associated with Triaenops afer and Hipposideros sp. bats that resulted in a NL-63 like virus, an ancestor of the human pathogen HCoV-NL63. These results suggest that inter-species recombination may play an important role in CoV evolution and the emergence of novel CoVs with zoonotic potential. |
Virology, immunology and pathology of human rabies during treatment.
Caicedo Y , Paez A , Kuzmin I , Niezgoda M , Orciari LA , Yager PA , Recuenco S , Franka R , Velasco-Villa A , Willoughby RE Jr . Pediatr Infect Dis J 2014 34 (5) 520-8 BACKGROUND: Rabies is an acute fatal encephalitis caused by all members of the Lyssavirus genus. The first human rabies survivor without benefit of prior vaccination was reported from Milwaukee in 2005. We report a second unvaccinated patient who showed early recovery from rabies and then died accidentally during convalescence, providing an unparalleled opportunity to examine the histopathology as well as immune and virological correlates of early recovery from human rabies. METHODS: Case report, rapid fluorescent focus inhibition test, enzyme-linked immunosorbent assay, indirect and direct fluorescent antibody assays, reverse-transcriptase polymerase chain reaction, phylogenetic reconstruction, isolation in tissue culture, pathology and immunohistochemistry. RESULTS: The 9 year old died 76 days after presenting with rabies of vampire bat phylogeny transmitted by cat bite. Antibody response in serum and CSF was robust and associated with severe cerebral edema. No rabies virus was cultured at autopsy. Rabies virus antigen was atypical in size and distribution. Rabies virus genome was present in neocortex but absent in brainstem. CONCLUSIONS:: Clinical recovery was associated with detection of neutralizing antibody and clearance of infectious rabies virus in the CNS by 76 days, but not clearance of detectable viral subcomponents such as nucleoprotein antigen or RNA in brain. |
Rabies in rodents and lagomorphs in the United States, 1995-2010
Fitzpatrick JL , Dyer JL , Blanton JD , Kuzmin IV , Rupprecht CE . J Am Vet Med Assoc 2014 245 (3) 333-7 OBJECTIVE: To assess the epidemiology of rabies in rodents and lagomorphs and provide information that will enable public health officials to make recommendations regarding postexposure prophylaxis for humans after contact with these animals. DESIGN: Cross-sectional epidemiological analysis. SAMPLE: Rodents and lagomorphs submitted to state laboratories for rabies diagnosis from 1995 through 2010. PROCEDURES: Positive samples were identified by use of direct fluorescent antibody testing, typed by sequencing of viral genes, and quantified via titration in mice or cell culture. RESULTS: 737 rabid rodents and lagomorphs were reported from 1995 through 2010, which represented a 62.3% increase, compared with the number of rabid rodents and lagomorphs reported from 1979 through 1994. The most commonly reported rodents or lagomorphs were groundhogs (Marmota monax). All animals submitted to the CDC for additional viral characterization were positive for the raccoon rabies virus variant. Infectious virus or viral RNA was detected in salivary glands or oral cavity tissues in 11 of 13 rabid rodents. CONCLUSIONS AND CLINICAL RELEVANCE: The increase in reported rabid rodents, compared with results of previous studies, appeared to be associated with spillover infections from the raccoon rabies epizootic during the first half of the study period. Analysis supported the assumption that rabies remained rare in rodents and lagomorphs. However, transmission of rabies virus via exposure to a rabid rodent or lagomorph may be possible. Given the rarity of rabies in these species, diagnostic testing and consideration of postexposure prophylaxis for humans with potential exposures should be considered on a case-by-case basis. |
Molecular detection of adenoviruses, rhabdoviruses, and paramyxoviruses in bats from Kenya.
Conrardy C , Tao Y , Kuzmin IV , Niezgoda M , Agwanda B , Breiman RF , Anderson LJ , Rupprecht CE , Tong S . Am J Trop Med Hyg 2014 91 (2) 258-266 We screened 217 bats of at least 20 species from 17 locations in Kenya during July and August of 2006 for the presence of adenovirus, rhabdovirus, and paramyxovirus nucleic acids using generic reverse transcription polymerase chain reaction (RT-PCR) and PCR assays. Of 217 bat fecal swabs examined, 4 bats were adenovirus DNA-positive, 11 bats were paramyxovirus RNA-positive, and 2 bats were rhabdovirus RNA-positive. Three bats were coinfected by two different viruses. By sequence comparison and phylogenetic analysis, the Kenya bat paramyxoviruses and rhabdoviruses from this study may represent novel viral lineages within their respective families; the Kenya bat adenoviruses could not be confirmed as novel, because the same region sequences from other known bat adenovirus genomes for comparison were lacking. Our study adds to previous evidence that bats carry diverse, potentially zoonotic viruses and may be coinfected with more than one virus. |
Phylogenetic and epidemiologic evidence of multiyear incubation in human rabies.
Boland TA , McGuone D , Jindal J , Rocha M , Cumming M , Rupprecht CE , Barbosa TF , de Novaes Oliveira R , Chu CJ , Cole AJ , Kotait I , Kuzmina NA , Yager PA , Kuzmin IV , Hedley-Whyte ET , Brown CM , Rosenthal ES . Ann Neurol 2014 75 (1) 155-60 Eight years after emigrating from Brazil, an otherwise healthy man developed rabies. An exposure prior to immigration was reported. Genetic analysis revealed a canine rabies virus variant found only in the patient's home country, and the patient had not traveled internationally since immigrating to the United States. We describe how epidemiological, phylogenetic, and viral sequencing data provided confirmation that rabies encephalomyelitis may present after a long, multiyear incubation period, a consideration that previously has been hypothesized without the ability to exclude a more recent exposure. Accordingly, rabies should be considered in the diagnosis of any acute encephalitis, myelitis, or encephalomyelitis. |
The phylogeography and spatiotemporal spread of south-central skunk rabies virus
Kuzmina NA , Lemey P , Kuzmin IV , Mayes BC , Ellison JA , Orciari LA , Hightower D , Taylor ST , Rupprecht CE . PLoS One 2013 8 (12) e82348 The south-central skunk rabies virus (SCSK) is the most broadly distributed terrestrial viral lineage in North America. Skunk rabies has not been efficiently targeted by oral vaccination campaigns and represents a natural system of pathogen invasion, yielding insights to rabies emergence. In the present study we reconstructed spatiotemporal spread of SCSK in the whole territory of its circulation using a combination of Bayesian methods. The analysis based on 241 glycoprotein gene sequences demonstrated that SCSK is much more divergent phylogenetically than was appreciated previously. According to our analyses the SCSK originated in the territory of Texas ~170 years ago, and spread geographically during the following decades. The wavefront velocity in the northward direction was significantly greater than in the eastward and westward directions. Rivers (except the Mississippi River and Rio Grande River) did not constitute significant barriers for epizootic spread, in contrast to deserts and mountains. The mean dispersal rate of skunk rabies was lower than that of the raccoon and fox rabies. Viral lineages circulate in their areas with limited evidence of geographic spread during decades. However, spatiotemporal reconstruction shows that after a long period of stability the dispersal rate and wavefront velocity of SCSK are increasing. Our results indicate that there is a need to develop control measures for SCSK, and suggest how such measure can be implemented most efficiently. Our approach can be extrapolated to other rabies reservoirs and used as a tool for investigation of epizootic patterns and planning interventions towards disease elimination. |
Isolation and molecular characterization of Fikirini rhabdovirus, a novel virus from a Kenyan bat.
Kading RC , Gilbert AT , Mossel EC , Crabtree MB , Kuzmin IV , Niezgoda M , Agwanda B , Markotter W , Weil MR , Montgomery JM , Rupprecht CE , Miller BR . J Gen Virol 2013 94 2393-8 Zoonotic and vector-borne pathogens have comprised a significant component of emerging human infections in recent decades, and bats are increasingly recognized as reservoirs for many of these disease agents. To identify novel pathogens associated with bats, we screened tissues of bats collected in Kenya. Virus isolates were identified by next generation sequencing of viral nucleic acid preparations from the infected cell culture supernatant and characterized. Here we report the identification of Fikirini rhabdovirus, a novel rhabdovirus isolated from a bat, Hipposideros vittatus, captured along the Kenyan coast. |
A reassessment of the evolutionary timescale of bat rabies viruses based upon glycoprotein gene sequences.
Kuzmina NA , Kuzmin IV , Ellison JA , Taylor ST , Bergman DL , Dew B , Rupprecht CE . Virus Genes 2013 47 (2) 305-10 Rabies, an acute progressive encephalomyelitis caused by viruses in the genus Lyssavirus, is one of the oldest known infectious diseases. Although dogs and other carnivores represent the greatest threat to public health as rabies reservoirs, it is commonly accepted that bats are the primary evolutionary hosts of lyssaviruses. Despite early historical documentation of rabies, molecular clock analyses indicate a quite young age of lyssaviruses, which is confusing. For example, the results obtained for partial and complete nucleoprotein gene sequences of rabies viruses (RABV), or for a limited number of glycoprotein gene sequences, indicated that the time of the most recent common ancestor (TMRCA) for current bat RABV diversity in the Americas lies in the seventeenth to eighteenth centuries and might be directly or indirectly associated with the European colonization. Conversely, several other reports demonstrated high genetic similarity between lyssavirus isolates, including RABV, obtained within a time interval of 25-50 years. In the present study, we attempted to re-estimate the age of several North American bat RABV lineages based on the largest set of complete and partial glycoprotein gene sequences compiled to date (n = 201) employing a codon substitution model. Although our results overlap with previous estimates in marginal areas of the 95 % high probability density (HPD), they suggest a longer evolutionary history of American bat RABV lineages (TMRCA at least 732 years, with a 95 % HPD 436-1107 years). |
Bats are a major natural reservoir for hepaciviruses and pegiviruses
Quan PL , Firth C , Conte JM , Williams SH , Zambrana-Torrelio CM , Anthony SJ , Ellison JA , Gilbert AT , Kuzmin IV , Niezgoda M , Osinubi MO , Recuenco S , Markotter W , Breiman RF , Kalemba L , Malekani J , Lindblade KA , Rostal MK , Ojeda-Flores R , Suzan G , Davis LB , Blau DM , Ogunkoya AB , Alvarez Castillo DA , Moran D , Ngam S , Akaibe D , Agwanda B , Briese T , Epstein JH , Daszak P , Rupprecht CE , Holmes EC , Lipkin WI . Proc Natl Acad Sci U S A 2013 110 (20) 8194-9 Although there are over 1,150 bat species worldwide, the diversity of viruses harbored by bats has only recently come into focus as a result of expanded wildlife surveillance. Such surveys are of importance in determining the potential for novel viruses to emerge in humans, and for optimal management of bats and their habitats. To enhance our knowledge of the viral diversity present in bats, we initially surveyed 415 sera from African and Central American bats. Unbiased high-throughput sequencing revealed the presence of a highly diverse group of bat-derived viruses related to hepaciviruses and pegiviruses within the family Flaviridae. Subsequent PCR screening of 1,258 bat specimens collected worldwide indicated the presence of these viruses also in North America and Asia. A total of 83 bat-derived viruses were identified, representing an infection rate of nearly 5%. Evolutionary analyses revealed that all known hepaciviruses and pegiviruses, including those previously documented in humans and other primates, fall within the phylogenetic diversity of the bat-derived viruses described here. The prevalence, unprecedented viral biodiversity, phylogenetic divergence, and worldwide distribution of the bat-derived viruses suggest that bats are a major and ancient natural reservoir for both hepaciviruses and pegiviruses and provide insights into the evolutionary history of hepatitis C virus and the human GB viruses. |
Conservation of binding epitopes for monoclonal antibodies on the rabies virus glycoprotein
Kuzmina NA , Kuzmin IV , Ellison JA , Rupprecht CE . J Antivir Antiretrovir 2013 5 (2) 037-043 The global need for rabies immune globulin (RIG) for post-exposure prophylaxis (PEP) is significant. The cost of RIG, either of equine or human origin, is prohibitive for most patients in developing countries. Limitations of supply may occur worldwide. Several virus-neutralizing monoclonal antibodies (MAbs), binding to the rabies virus glycoprotein have been proposed as a replacement of conventional RIG in human PEP due to the ability of largescale production at a reduced cost. In the present study we analyzed 1,042 rabies virus glycoprotein sequences, generated de novo and retrieved from GenBank, to determine the conservation of binding epitopes for several well characterized rabies virus-neutralizing MAbs. Our analysis demonstrated that the use of a single MAb for rabies PEPis inappropriate, because certain viral sequences had critical amino acid substitutions in binding epitopes for each MAb. Rather, a cocktail of MAbs, targeting non-overlapping epitopes, offers a reliable alternative, as no sequences from our study harbored critical substitutions in binding sites for two or more MAbs simultaneously. (2013 Kuzmina NA, et al.) |
Discovery of diverse polyomaviruses in bats and the evolutionary history of the Polyomaviridae
Tao Y , Shi M , Conrardy C , Kuzmin IV , Recuenco S , Agwanda B , Alvarez DA , Ellison JA , Gilbert AT , Moran D , Niezgoda M , Lindblade KA , Holmes EC , Breiman RF , Rupprecht CE , Tong S . J Gen Virol 2013 94 738-48 Polyomaviruses (PyVs) have been identified in a wide range of avian and mammalian species. However, little is known about their occurrence, genetic diversity and evolutionary history in bats, even though bats are important reservoirs for many emerging viral pathogens. This study screened 380 specimens from 35 bat species from Kenya and Guatemala for the presence of PyVs by semi-nested pan-PyV PCR assays. PyV DNA was detected in 24 of the 380 bat specimens. Phylogenetic analysis revealed that the bat PyV sequences formed 12 distinct lineages. Full-genome sequences were obtained for seven representative lineages and possessed similar genomic features to known PyVs. Strikingly, this evolutionary analysis revealed that the bat PyVs were paraphyletic, suggestive of multiple species jumps between bats and other mammalian species, such that the theory of virus-host co-divergence for mammalian PyVs as a whole could be rejected. In addition, evidence was found for strong heterogeneity in evolutionary rate and potential recombination in a number of PyV complete genomes, which complicates both phylogenetic analysis and virus classification. In summary, this study revealed that bats are important reservoirs of PyVs and that these viruses have a complex evolutionary history. |
Complete genome sequence of Ikoma lyssavirus.
Marston DA , Ellis RJ , Horton DL , Kuzmin IV , Wise EL , McElhinney LM , Banyard AC , Ngeleja C , Keyyu J , Cleaveland S , Lembo T , Rupprecht CE , Fooks AR . J Virol 2012 86 (18) 10242-3 Lyssaviruses (family Rhabdoviridae) constitute one of the most important groups of viral zoonoses globally. All lyssaviruses cause the disease rabies, an acute progressive encephalitis for which, once symptoms occur, there is no effective cure. Currently available vaccines are highly protective against the predominantly circulating lyssavirus species. Using next-generation sequencing technologies, we have obtained the whole-genome sequence for a novel lyssavirus, Ikoma lyssavirus (IKOV), isolated from an African civet in Tanzania displaying clinical signs of rabies. Genetically, this virus is the most divergent within the genus Lyssavirus. Characterization of the genome will help to improve our understanding of lyssavirus diversity and enable investigation into vaccine-induced immunity and protection. |
Molecular inferences suggest multiple host shifts of rabies viruses from bats to mesocarnivores in Arizona during 2001-2009
Kuzmin IV , Shi M , Orciari LA , Yager PA , Velasco-Villa A , Kuzmina NA , Streicker DG , Bergman DL , Rupprecht CE . PLoS Pathog 2012 8 (6) e1002786 In nature, rabies virus (RABV; genus Lyssavirus, family Rhabdoviridae) represents an assemblage of phylogenetic lineages, associated with specific mammalian host species. Although it is generally accepted that RABV evolved originally in bats and further shifted to carnivores, mechanisms of such host shifts are poorly understood, and examples are rarely present in surveillance data. Outbreaks in carnivores caused by a RABV variant, associated with big brown bats, occurred repeatedly during 2001-2009 in the Flagstaff area of Arizona. After each outbreak, extensive control campaigns were undertaken, with no reports of further rabies cases in carnivores for the next several years. However, questions remained whether all outbreaks were caused by a single introduction and further perpetuation of bat RABV in carnivore populations, or each outbreak was caused by an independent introduction of a bat virus. Another question of concern was related to adaptive changes in the RABV genome associated with host shifts. To address these questions, we sequenced and analyzed 66 complete and 20 nearly complete RABV genomes, including those from the Flagstaff area and other similar outbreaks in carnivores, caused by bat RABVs, and representatives of the major RABV lineages circulating in North America and worldwide. Phylogenetic analysis demonstrated that each Flagstaff outbreak was caused by an independent introduction of bat RABV into populations of carnivores. Positive selection analysis confirmed the absence of post-shift changes in RABV genes. In contrast, convergent evolution analysis demonstrated several amino acids in the N, P, G and L proteins, which might be significant for pre-adaptation of bat viruses to cause effective infection in carnivores. The substitution S/T(242) in the viral glycoprotein is of particular merit, as a similar substitution was suggested for pathogenicity of Nishigahara RABV strain. Roles of the amino acid changes, detected in our study, require additional investigations, using reverse genetics and other approaches. |
Immune response after rabies vaccine in a kidney transplant recipient
Rodriguez-Romo R , Morales-Buenrostro LE , Lecuona L , Escalante-Santillan N , Velasco-Villa A , Kuzmin I , Rupprecht CE , De-Leo C , Ramirez J , Alberu J . Transpl Infect Dis 2011 13 (5) 492-5 A 48-year-old male kidney-transplant recipient was bitten by a rabid dog. His immunosuppressive treatment consisted of cyclosporine 60 mg b.i.d., mycophenolate mofetil (MMF) 250 mg t.i.d., and prednisone 5 mg. After wound care, he received 5 doses of purified vero cell rabies vaccine on days 0, 3, 7, 14, and 28, and human rabies immunoglobulin, according to international guidelines. Adequate levels of rabies virus neutralizing antibodies were observed after the administration of the third vaccine dose. However, a decrease of antibody titer was detected by day 28. Immunosuppressive medication was minimized, withdrawing MMF and reducing the dose of cyclosporine. Booster doses of the same vaccine were administered on days 38, 41, 45, 52, and 66. Adequate neutralizing antibody response was recovered during the ensuing 12 months, under reduced immunosuppression. Nineteen months after the incident, the patient remains with good graft function and is asymptomatic for rabies. It remains to be determined whether the attained immune response was either the result of the booster vaccinations or the reduction of immunosuppression alone. Nevertheless, such an outcome would have been possible only with the combined management strategy implemented. |
Commerson's leaf-nosed bat (Hipposideros commersoni) is the likely reservoir of Shimoni bat virus
Kuzmin IV , Turmelle AS , Agwanda B , Markotter W , Niezgoda M , Breiman RF , Rupprecht CE . Vector Borne Zoonotic Dis 2011 11 (11) 1465-70 In this study we attempted to identify whether Commerson's leaf-nosed bat (Hipposideros commersoni) is the reservoir of Shimoni bat virus (SHIBV), which was isolated from a bat of this species in 2009. An alternative explanation is that the isolation of SHIBV from H. commersoni was a result of spill-over infection from other species, particularly from the Egyptian fruit bats (Rousettus aegyptiacus), which frequently sympatrically roost with H. commersoni and are known as the reservoir of the phylogenetically related Lagos bat virus (LBV). To evaluate these hypotheses, 769 bats of at least 17 species were sampled from 18 locations across Kenya during 2009-2010. Serum samples were subjected to virus neutralization tests against SHIBV and LBV. A limited amount of cross-neutralization between LBV and SHIBV was detected. However, H. commersoni bats demonstrated greater seroprevalence to SHIBV than to LBV, and greater virus-neutralizing titers to SHIBV than to LBV, with a mean difference of 1.16 log(10) (95% confidence intervals [CI]: 0.94-1.40; p<0.001). The opposite pattern was observed for sera of R. aegyptiacus bats, with a mean titer difference of 1.06 log(10) (95% CI: 0.83-1.30; p<0.001). Moreover, the seroprevalence in H. commersoni to SHIBV in the cave where these bats sympatrically roosted with R. aegyptiacus (and where SHIBV was isolated in 2009) was similar to their seroprevalence to SHIBV in a distant cave where no R. aegyptiacus were present (18.9% and 25.0%, respectively). These findings suggest that H. commersoni is the host species of SHIBV. Additional surveillance is needed to better understand the ecology of this virus and the potential risks of infection to humans and other mammalian species. |
Reassortant group A rotavirus from straw-colored fruit bat (Eidolon helvum)
Esona MD , Mijatovic-Rustempasic S , Conrardy C , Tong S , Kuzmin IV , Agwanda B , Breiman RF , Banyai K , Niezgoda M , Rupprecht CE , Gentsch JR , Bowen MD . Emerg Infect Dis 2010 16 (12) 1844-1852 Bats are known reservoirs of viral zoonoses. We report genetic characterization of a bat rotavirus (Bat/KE4852/07) detected in the feces of a straw-colored fruit bat (Eidolon helvum). Six bat rotavirus genes (viral protein [VP] 2, VP6, VP7, nonstructural protein [NSP] 2, NSP3, and NSP5) shared ancestry with other mammalian rotaviruses but were distantly related. The VP4 gene was nearly identical to that of human P[6] rotavirus strains, and the NSP4 gene was closely related to those of previously described mammalian rotaviruses, including human strains. Analysis of partial sequence of the VP1 gene indicated that it was distinct from cognate genes of other rotaviruses. No sequences were obtained for the VP3 and NSP1 genes of the bat rotavirus. This rotavirus was designated G25-P[6]-I15-R8(provisional)-C8-Mx-Ax-N8-T11-E2-H10. Results suggest that several reassortment events have occurred between human, animal, and bat rotaviruses. Several additional rotavirus strains were detected in bats. |
Bartonella spp. in bats, Kenya
Kosoy M , Bai Y , Lynch T , Kuzmin IV , Niezgoda M , Franka R , Agwanda B , Breiman RF , Rupprecht CE . Emerg Infect Dis 2010 16 (12) 1875-1881 We report the presence and diversity of Bartonella spp. in bats of 13 insectivorous and frugivorous species collected from various locations across Kenya. Bartonella isolates were obtained from 23 Eidolon helvum, 22 Rousettus aegyptiacus, 4 Coleura afra, 7 Triaenops persicus, 1 Hipposideros commersoni, and 49 Miniopterus spp. bats. Sequence analysis of the citrate synthase gene from the obtained isolates showed a wide assortment of Bartonella strains. Phylogenetically, isolates clustered in specific host bat species. All isolates from R. aegyptiacus, C. afra, and T. persicus bats clustered in separate monophyletic groups. In contrast, E. helvum and Miniopterus spp. bats harbored strains that clustered in several groups. Further investigation is needed to determine whether these agents are responsible for human illnesses in the region. |
Quantifying antigenic relationships among the Lyssaviruses
Horton DL , McElhinney LM , Marston DA , Wood JL , Russell CA , Lewis N , Kuzmin IV , Fouchier RA , Osterhaus AD , Fooks AR , Smith DJ . J Virol 2010 84 (22) 11841-8 All lyssaviruses cause fatal encephalitis in mammals. There is sufficient antigenic variation within the genus to cause variable vaccine efficacy but this variation is difficult to characterize quantitatively: sequence analysis cannot yet provide detailed antigenic information, and antigenic neutralization data have been refractory to high-resolution robust interpretation. Here, we address these issues by using state-of-the-art antigenic analyses to generate a high-resolution antigenic map of a global panel of 25 lyssaviruses. We compared the calculated antigenic distances with viral glycoprotein ectodomain sequence data. Although 67% of antigenic variation was predictable from glycoprotein amino acid sequence, there are in some cases substantial differences between genetic and antigenic distances thus highlighting the risk of inferring antigenic relationships solely from sequence data at this time. These differences included epidemiologically important antigenic differences between vaccine strains and wild-type rabies viruses. Further, we quantitatively assessed the antigenic relationships measured by rabbit, mouse, and human sera, validating the use of non-human experimental animals as a model for determining antigenic variation in humans. Passive immune globulin use is a crucial component of rabies post-exposure prophylaxis, and here we also show that it is possible to predict the reactivity of immune globulin against divergent lyssaviruses. |
Host phylogeny constrains cross-species emergence and establishment of rabies virus in bats
Streicker DG , Turmelle AS , Vonhof MJ , Kuzmin IV , McCracken GF , Rupprecht CE . Science 2010 329 (5992) 676-9 For RNA viruses, rapid viral evolution and the biological similarity of closely related host species have been proposed as key determinants of the occurrence and long-term outcome of cross-species transmission. Using a data set of hundreds of rabies viruses sampled from 23 North American bat species, we present a general framework to quantify per capita rates of cross-species transmission and reconstruct historical patterns of viral establishment in new host species using molecular sequence data. These estimates demonstrate diminishing frequencies of both cross-species transmission and host shifts with increasing phylogenetic distance between bat species. Evolutionary constraints on viral host range indicate that host species barriers may trump the intrinsic mutability of RNA viruses in determining the fate of emerging host-virus interactions. |
Evidence of Lagos bat virus circulation among Nigerian fruit bats
Dzikwi AA , Kuzmin II , Umoh JU , Kwaga JK , Ahmad AA , Rupprecht CE . J Wildl Dis 2010 46 (1) 267-71 During lyssavirus surveillance, 350 brains from four species of fruit bats and one species of insectivorous bat were collected from seven locations in Northern Nigeria during May to October, 2006. Lyssavirus antigen was not detected in the brains, and isolation attempts in mice were unsuccessful. However, serologic tests demonstrated the presence of lyssavirus-neutralizing antibodies in bat sera. Of 140 sera tested, 27 (19%) neutralized Lagos bat virus, and two of these additionally neutralized Mokola virus. The positive samples originated from the straw-colored fruit bat (Eidolon helvum) and the Gambian epaulet bat (Epomophorus gambianus). No neutralizing activity was detected against other lyssaviruses including rabies, Duvenhage, and West Caucasian bat viruses. |
Shimoni bat virus, a new representative of the Lyssavirus genus
Kuzmin IV , Mayer AE , Niezgoda M , Markotter W , Agwanda B , Breiman RF , Rupprecht CE . Virus Res 2010 149 (2) 197-210 During 2009, 616 bats representing at least 22 species were collected from 10 locations throughout Kenya. A new lyssavirus, named Shimoni bat virus (SHIBV), was isolated from the brain of a dead Commerson's leaf-nosed bat (Hipposideros commersoni), found in a cave in the coastal region of Kenya. Genetic distances and phylogenetic reconstructions, implemented for each gene and for the concatenated alignment of all five structural genes (N, P, M, G and L), demonstrated that SHIBV cannot be identified with any of the existing species, but rather should be considered an independent species within phylogroup II of the Lyssavirus genus, most similar to Lagos bat virus (LBV). Antigenic reaction patterns with anti-nucleocapsid monoclonal antibodies corroborated these distinctions. In addition, new data on the diversity of LBV suggests that this species may be subdivided quantitatively into three separate genotypes. However, the identity values alone are not considered sufficient criteria for demarcation of new species within LBV. |
Lagos bat virus virulence in mice inoculated by the peripheral route
Markotter W , Kuzmin IV , Rupprecht CE , Nel LH . Epidemiol Infect 2009 137 (8) 1155-62 Lagos bat virus (LBV) constitutes genotype (gt) 2 in the Lyssavirus genus. In contrast to the gt1 lyssavirus, rabies virus (RABV), LBV was reported to have markedly reduced levels of peripheral pathogenicity. However, this opinion was based on a study of one isolate of LBV only and the reduction in pathogenicity was essentially attributed to the amino-acid substitution at position 333 of glycoprotein ectodomain. In the present study we have demonstrated that peripheral pathogenicity of representatives of LBV in a murine model is as high as that of RABV. Comparison of amino-acid substitutions among the viral glycoproteins, demonstrated significant differences within two antigenic sites between different phylogenetic lineages of LBV. Such molecular variability potentially contributes to differences in peripheral pathogenicity of lyssaviruses. |
The rhabdoviruses: biodiversity, phylogenetics, and evolution
Kuzmin IV , Novella IS , Dietzgen RG , Padhi A , Rupprecht CE . Infect Genet Evol 2009 9 (4) 541-53 Rhabdoviruses (family Rhabdoviridae) include a diversity of important pathogens of animals and plants. They share morphology and genome organization. The understanding of rhabdovirus phylogeny, ecology and evolution has progressed greatly during the last 30 years, due to enhanced surveillance and improved methodologies of molecular characterization. Along with six established genera, several phylogenetic groups at different levels were described within the Rhabdoviridae. However, comparative relationships between viral phylogeny and taxonomy remains incomplete, with multiple representatives awaiting further genetic characterization. The same is true for rhabdovirus evolution. To date, rather simplistic molecular clock models only partially describe the evolutionary dynamics of postulated viral lineages. Ongoing progress in viral evolutionary and ecological investigations will provide the platform for future studies of this diverse family. |
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