Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-22 (of 22 Records) |
Query Trace: Ting J[original query] |
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Genome-wide patterns of gene expression in a wild primate indicate species-specific mechanisms associated with tolerance to natural simian immunodeficiency virus infection (preprint)
Simons ND , Eick GN , Ruiz-Lopez MJ , Hyeroba D , Omeja PA , Weny G , Chapman CA , Goldberg TL , Zheng H , Shankar A , Switzer WM , Frost SDW , Jones JH , Sterner KN , Ting N . bioRxiv 2018 395152 Over 40 species of nonhuman primates host simian immunodeficiency viruses (SIVs). In natural hosts, infection is generally assumed to be nonpathogenic due to a long coevolutionary history between host and virus, although pathogenicity is difficult to study in wild nonhuman primates. We used whole-blood RNA-seq and SIV prevalence from 29 wild Ugandan red colobus (Piliocolobus tephrosceles) to assess the effects of SIV infection on host gene expression in wild, naturally SIV-infected primates. We found no evidence for chronic immune activation in infected individuals, suggesting that SIV is not immunocompromising in this species, in contrast to HIV in humans. Notably, an immunosuppressive gene, CD101, was upregulated in infected individuals. This gene has not been previously described in the context of nonpathogenic SIV infection. This expands the known variation associated with SIV infection in natural hosts, and may suggest a novel mechanism for tolerance of SIV infection in the Ugandan red colobus. |
SARS-CoV-2 case detection using community event-based surveillance system-February-September 2020: lessons learned from Senegal
Seck O , Loko Roka J , Ndiaye M , Namageyo-Funa A , Abdoulaye S , Mangane A , Dieye NL , Ndoye B , Diop B , Ting J , Pasi O . BMJ Glob Health 2023 8 (6) The COVID-19 pandemic necessitated the rapid development and implementation of effective surveillance systems to detect and respond to the outbreak in Senegal. In this documentation, we describe the design and implementation of the Community Event-Based Surveillance (CEBS) system in Senegal to strengthen the existing Integrated Disease Surveillance and Response system. The CEBS system used a hotline and toll-free number to collect and triage COVID-19-related calls from the community. Data from the CEBS system were integrated with the national system for further investigation and laboratory testing. From February to September 2020, a total of 10 760 calls were received by the CEBS system, with 10 751 calls related to COVID-19. The majority of calls came from the Dakar region, which was the epicentre of the outbreak in Senegal. Of the COVID-19 calls, 50.2% were validated and referred to health districts for further investigation, and 25% of validated calls were laboratory-confirmed cases of SARS-CoV-2. The implementation of the CEBS system allowed for timely detection and response to potential COVID-19 cases, contributing to the overall surveillance efforts in the country. Lessons learned from this experience include the importance of decentralised CEBS, population sensitisation on hotlines and toll-free usage, and the potential role of Community Health Workers in triaging alerts that needs further analysis. This experience highlights the contribution of a CEBS system in Senegal and provides insights into the design and operation of such a system. The findings can inform other countries in strengthening their surveillance systems and response strategies. |
Estimating burden of syphilis among men who have sex with men - Authors' reply
Chico RM , Tsuboi M , Evans J , Davies EP , Rowley J , Korenromp EL , Clayton T , Mabey D , Taylor MM . Lancet Glob Health 2021 9 (12) e1649 Can a change in venues sampled in syphilis serosurveys influence prevalence estimates among men who have sex with men (MSM), and has this contributed to spurious trends of decline in the past decade? In this issue of The Lancet Global Health, Ting-Ting Jiang and colleagues in their Correspondence pose this question and note evidence from China that HIV prevalence evaluated among MSM at public bathhouses and saunas is consistently higher than among MSM recruited through internet sites.1 This difference in testing venues could extend to syphilis, although such a difference was not apparent in our recent global systematic review and meta-analysis of syphilis prevalence among MSM published in The Lancet Global Health.2 In our study, the pooled prevalence estimate of syphilis among studies that recruited MSM at venues including bathhouses and saunas, clubs, and one-off public events was 6·1% (95% CI 3·7–9·1; 13 229 MSM; 29 data points). When taking into account MSM studies that used a variety of convenience sampling methods, including internet advertising, the pooled prevalence estimate was 8·7% (95% CI 7·6–9·9%; 109 065 MSM; 64 data points). Neither of these subgroup estimates were meaningfully different from our overall pooled estimate of 7·5% (95% CI 7·0–8·0; 606 232 MSM; 345 data points). However, a prevalence data compilation and trend estimation of syphilis in Yunnan province, China did find prevalence among MSM (or female sex workers) to be systematically lower in routine annual surveillance surveys and higher in research studies.3 The venues involved might have contributed to this difference, although neither dataset (nor their weighted sum) showed a statistically significant upward or downward prevalence trend over 2010–17; these findings do highlight the importance of inferring time trends only within series of methodologically comparable samples. |
Seroprevalence of anti-SARS-CoV-2 antibodies in Senegal: a national population-based cross-sectional survey, between October and November 2020.
Talla C , Loucoubar C , Roka JL , Barry MA , Ndiaye S , Diarra M , Thiam MS , Faye O , Dia M , Diop M , Ndiaye O , Tall A , Faye R , Mbow AA , Diouf B , Diallo JP , Keita IM , Ndiaye M , Woudenberg T , White M , Ting J , Diagne CT , Pasi O , Diop B , Sall AA , Vigan-Womas I , Faye O . IJID Reg 2022 3 117-125 OBJECTIVES: A nationwide cross-sectional epidemiological survey was conducted to capture the true extent of coronavirus disease 2019 (COVID-19) exposure in Senegal. METHODS: Multi-stage random cluster sampling of households was performed between October and November 2020, at the end of the first wave of COVID-19 transmission. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were screened using three distinct ELISA assays. Adjusted prevalence rates for the survey design were calculated for each test separately, and thereafter combined. Crude and adjusted prevalence rates based on test performance were estimated to assess the seroprevalence. As some samples were collected in high malaria endemic areas, the relationship between SARS-CoV-2 seroreactivity and antimalarial humoral immunity was also investigated. RESULTS: Of the 1463 participants included in this study, 58.8% were female and 41.2% were male; their mean age was 29.2 years (range 0.20-84.8.0 years). The national seroprevalence was estimated at 28.4% (95% confidence interval 26.1-30.8%). There was substantial regional variability. All age groups were impacted, and the prevalence of SARS-CoV-2 was comparable in the symptomatic and asymptomatic groups. An estimated 4 744 392 (95% confidence interval 4 360 164-5 145 327) were potentially infected with SARS-CoV-2 in Senegal, while 16 089 COVID-19 RT-PCR laboratory-confirmed cases were reported by the national surveillance. No correlation was found between SARS-CoV-2 and Plasmodium seroreactivity. CONCLUSIONS: These results provide a better estimate of SARS-CoV-2 dissemination in the Senegalese population. Preventive and control measures need to be reinforced in the country and especially in the south border regions. |
SPECIAL REPORT: A standardized definition of placental infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a consensus statement from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH/NICHD) SARS-CoV-2 placental infection workshop.
Roberts DJ , Edlow AG , Romero RJ , Coyne CB , Ting DT , Hornick JL , Zaki SR , Adhikari UD , Serghides L , Gaw SL , Metz TD . Am J Obstet Gynecol 2021 225 (6) 593 e1-593 e9 Pregnant individuals infected with SARS-CoV-2 have higher rates of ICU admission, oxygen requirement, need for mechanical ventilation and death than non-pregnant individuals. Increased COVID-19 disease severity may be associated with increased risk for viremia and placental infection. Maternal SARS-CoV-2 infection is also associated with pregnancy complications such as preeclampsia and preterm birth, that can be either placentally-mediated or reflected in the placenta. Maternal viremia followed by placental infection may lead to maternal-fetal transmission (vertical), which affects 1-3% of exposed newborns. However, there is no agreed-upon or standard definition of placental infection. NIH/NICHD convened a group of experts to propose a working definition of placental infection to inform ongoing studies of SARS-CoV-2 during pregnancy. Experts recommended that placental infection be defined using techniques that allow virus detection and localization in placental tissue by one or more of the following methods: in-situ hybridization with anti-sense probe (detects replication) and/or a sense probe (detects viral genome or immunohistochemistry to detect viral nucleocapsid (N) or spike (S) proteins. If the above methods are not possible, RT-PCR detection and/or quantification of viral RNA in placental homogenates, or electron microscopy are alternative approaches. A graded classification for the likelihood of placental infection as definitive, probable, possible, and unlikely was proposed. Manuscripts reporting placental infection should describe the sampling method (location and number of samples collected), method of preservation of tissue, and detection technique. Recommendations were made for the handling of the placenta, examination, and sampling, as well as the use of validated reagents and sample protocols (included as appendices). |
Reactive astrocyte nomenclature, definitions, and future directions.
Escartin C , Galea E , Lakatos A , O'Callaghan JP , Petzold GC , Serrano-Pozo A , Steinhäuser C , Volterra A , Carmignoto G , Agarwal A , Allen NJ , Araque A , Barbeito L , Barzilai A , Bergles DE , Bonvento G , Butt AM , Chen WT , Cohen-Salmon M , Cunningham C , Deneen B , De Strooper B , Díaz-Castro B , Farina C , Freeman M , Gallo V , Goldman JE , Goldman SA , Götz M , Gutiérrez A , Haydon PG , Heiland DH , Hol EM , Holt MG , Iino M , Kastanenka KV , Kettenmann H , Khakh BS , Koizumi S , Lee CJ , Liddelow SA , MacVicar BA , Magistretti P , Messing A , Mishra A , Molofsky AV , Murai KK , Norris CM , Okada S , Oliet SHR , Oliveira JF , Panatier A , Parpura V , Pekna M , Pekny M , Pellerin L , Perea G , Pérez-Nievas BG , Pfrieger FW , Poskanzer KE , Quintana FJ , Ransohoff RM , Riquelme-Perez M , Robel S , Rose CR , Rothstein JD , Rouach N , Rowitch DH , Semyanov A , Sirko S , Sontheimer H , Swanson RA , Vitorica J , Wanner IB , Wood LB , Wu J , Zheng B , Zimmer ER , Zorec R , Sofroniew MV , Verkhratsky A . Nat Neurosci 2021 24 (3) 312-325 Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions. |
Distinct amino acid and lipid perturbations characterize acute versus chronic malaria.
Cordy RJ , Patrapuvich R , Lili LN , Cabrera-Mora M , Chien JT , Tharp GK , Khadka M , Meyer EV , Lapp SA , Joyner CJ , Garcia A , Banton S , Tran V , Luvira V , Rungin S , Saeseu T , Rachaphaew N , Pakala SB , DeBarry JD , Kissinger JC , Ortlund EA , Bosinger SE , Barnwell JW , Jones DP , Uppal K , Li S , Sattabongkot J , Moreno A , Galinski MR . JCI Insight 2019 4 (9) Chronic malaria is a major public health problem and significant challenge for disease eradication efforts. Despite its importance, the biological factors underpinning chronic malaria are not fully understood. Recent studies have shown that host metabolic state can influence malaria pathogenesis and transmission, but its role in chronicity is not known. Here, with the goal of identifying distinct modifications in the metabolite profiles of acute versus chronic malaria, metabolomics was performed on plasma from Plasmodium-infected humans and nonhuman primates with a range of parasitemias and clinical signs. In rhesus macaques infected with Plasmodium coatneyi, significant alterations in amines, carnitines, and lipids were detected during a high parasitemic acute phase and many of these reverted to baseline levels once a low parasitemic chronic phase was established. Plasmodium gene expression, studied in parallel in the macaques, revealed transcriptional changes in amine, fatty acid, lipid and energy metabolism genes, as well as variant antigen genes. Furthermore, a common set of amines, carnitines, and lipids distinguished acute from chronic malaria in plasma from human Plasmodium falciparum cases. In summary, distinct host-parasite metabolic environments have been uncovered that characterize acute versus chronic malaria, providing insights into the underlying host-parasite biology of malaria disease progression. |
Genome-wide patterns of gene expression in a wild primate indicate species-specific mechanisms associated with tolerance to natural simian immunodeficiency virus infection.
Simons ND , Eick GN , Ruiz-Lopez MJ , Hyeroba D , Omeja PA , Weny G , Chapman CA , Goldberg TL , Zheng H , Shankar A , Switzer WM , Frost SDW , Jones JH , Sterner KN , Ting N . Genome Biol Evol 2019 11 (6) 1630-1643 Over 40 species of nonhuman primates host simian immunodeficiency viruses (SIVs). In natural hosts, infection is generally assumed to be nonpathogenic due to a long coevolutionary history between host and virus, although pathogenicity is difficult to study in wild nonhuman primates. We used whole-blood RNA-seq and SIV prevalence from 29 wild Ugandan red colobus (Piliocolobus tephrosceles) to assess the effects of SIV infection on host gene expression in wild, naturally SIV-infected primates. We found no evidence for chronic immune activation in infected individuals, suggesting that SIV is not immunocompromising in this species, in contrast to HIV in humans. Notably, an immunosuppressive gene, CD101, was upregulated in infected individuals. This gene has not been previously described in the context of nonpathogenic SIV infection. This expands the known variation associated with SIV infection in natural hosts, and may suggest a novel mechanism for tolerance of SIV infection in the Ugandan red colobus. |
Genetic indicators of drug resistance in the highly repetitive genome of Trichomonas vaginalis.
Bradic M , Warring SD , Tooley GE , Scheid P , Secor WE , Land KM , Huang PJ , Chen TW , Lee CC , Tang P , Sullivan SA , Carlton JM . Genome Biol Evol 2017 9 (6) 1658-1672 Trichomonas vaginalis, the most common non-viral sexually transmitted parasite, causes approximately 283 million trichomoniasis infections annually and is associated with pregnancy complications and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but in a fraction of clinical cases, the parasites can become resistant to this drug. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance. Reduced representation genome sequencing of approximately 100 T. vaginalis clinical isolates identified 3,923 SNP markers and presence of a bipartite population structure. Linkage disequilibrium was found to decay rapidly, suggesting genome-wide recombination and the feasibility of genetic association studies in the parasite. We identified 72 SNPs associated with metronidazole resistance, and a comparison of SNPs within several lab-derived resistant lines revealed an overlap with the clinically resistant isolates. We identified SNPs in genes for which no function has yet been assigned, as well as in functionally-characterized genes relevant to drug resistance (e.g., pyruvate:ferredoxin oxidoreductase). Transcription profiles of resistant strains showed common changes in genes involved in drug activation (e.g., flavin reductase), accumulation (e.g., multidrug resistance pump), and detoxification (e.g., nitroreductase). Finally, we identified convergent genetic changes in lab-derived resistant lines of Tritrichomonas foetus, a distantly-related species that causes venereal disease in cattle. Shared genetic changes within and between T. vaginalis and Tr. foetus parasites suggest conservation of the pathways through which adaptation has occurred. These findings extend our knowledge of drug resistance in the parasite, providing a panel of markers that can be used as a diagnostic tool. |
Hepatitis E in Singapore: A Case-Series and Viral Phylodynamics Study.
Teo EC , Tan BH , Purdy MA , Wong PS , Ting PJ , Chang PJ , Oon LL , Sue A , Teo CG , Tan CK . Am J Trop Med Hyg 2017 96 (4) 922-928 The incidence of hepatitis E in Singapore appears to be increasing. A retrospective case-series study of patients diagnosed with hepatitis E in a tertiary hospital from 2009 to 2013 was conducted. Of 16 cases, eight (50%) were solid-organ transplant recipients (SOTRs), and 14 (88%) were found infected by genotype 3 hepatitis E virus (HEV-3). Bayesian inferences based on HEV subgenomic sequences from seven cases suggest that HEV-3 strains were introduced to Singapore as two principal lineages. Within limitations of the study, it can be inferred that one lineage, in the 3efg clade, emerged about 83 years ago, probably originating from Japan, whereas the other, in the 3abchij clade, emerged about 40 years ago, from the United States. Establishment and subsequent transmissions of strains from these two lineages likely contribute to the current endemicity of hepatitis E in Singapore. |
High-Quality Genome Assembly and Annotation for Plasmodium coatneyi, Generated Using Single-Molecule Real-Time PacBio Technology.
Chien JT , Pakala SB , Geraldo JA , Lapp SA , Humphrey JC , Barnwell JW , Kissinger JC , Galinski MR . Genome Announc 2016 4 (5) Plasmodium coatneyi is a protozoan parasite species that causes simian malaria and is an excellent model for studying disease caused by the human malaria parasite, P. falciparum Here we report the complete (nontelomeric) genome sequence of P. coatneyi Hackeri generated by the application of only Pacific Biosciences RS II (PacBio RS II) single-molecule real-time (SMRT) high-resolution sequence technology and assembly using the Hierarchical Genome Assembly Process (HGAP). This is the first Plasmodium genome sequence reported to use only PacBio technology. This approach has proven to be superior to short-read only approaches for this species. |
Assessing commitment and reporting fidelity to a text message-based participatory surveillance in rural Western Uganda
Lester J , Paige S , Chapman CA , Gibson M , Holland Jones J , Switzer WM , Ting N , Goldberg TL , Frost SD . PLoS One 2016 11 (6) e0155971 Syndromic surveillance, the collection of symptom data from individuals prior to or in the absence of diagnosis, is used throughout the developed world to provide rapid indications of outbreaks and unusual patterns of disease. However, the low cost of syndromic surveillance also makes it highly attractive for the developing world. We present a case study of electronic participatory syndromic surveillance, using participant-mobile phones in a rural region of Western Uganda, which has a high infectious disease burden, and frequent local and regional outbreaks. Our platform uses text messages to encode a suite of symptoms, their associated durations, and household disease burden, and we explore the ability of participants to correctly encode their symptoms, with an average of 75.2% of symptom reports correctly formatted between the second and 11th reporting timeslots. Concomitantly we identify divisions between participants able to rapidly adjust to this unusually participatory style of data collection, and those few for whom the study proved more challenging. We then perform analyses of the resulting syndromic time series, examining the clustering of symptoms by time and household to identify patterns such as a tendency towards the within-household sharing of respiratory illness. |
Cold Chain and Virus Free chloroplast-made Booster Vaccine to Confer Immunity Against Different Polio Virus Serotypes.
Chan HT , Xiao Y , Weldon WC , Oberste SM , Chumakov K , Daniell H . Plant Biotechnol J 2016 14 (11) 2190-2200 The WHO recommends complete withdrawal of Oral Polio Vaccine (OPV) Type 2 by April 2016 globally and replacing with at least one dose of Inactivated Poliovirus Vaccine (IPV). However, high-cost, limited supply of IPV, persistent circulating vaccine-derived polioviruses transmission and need for subsequent boosters remain unresolved. To meet this critical need, a novel strategy of a low cost cold-chain free plant-made viral protein 1 (VP1) subunit oral booster vaccine after single IPV dose is reported. Codon optimization of the VP1 gene enhanced expression by 50-fold in chloroplasts. Oral boosting of VP1 expressed in plant cells with plant-derived adjuvants after single priming with IPV significantly increased VP1-IgG1 and VP1-IgA titers when compared to lower IgG1 or negligible IgA titers with IPV injections. IgA plays a pivotal role in polio eradication because of its transmission through contaminated water or sewer systems. Neutralizing antibody titers (~3.17-10.17 log2 titer) and serpositivity (70-90%) against all three poliovirus Sabin serotypes were observed with two doses of IPV and plant-cell oral boosters but single dose of IPV resulted in poor neutralization. Lyophilized plant cells expressing VP1 stored at ambient temperature maintained efficacy and preserved antigen folding/assembly indefinitely, thereby eliminating cold-chain currently required for all vaccines. Replacement of OPV with this booster vaccine and the next steps in clinical translation of FDA approved antigens and adjuvants are discussed. |
Genomic resources notes accepted 1 December 2014 - 31 January 2015.
Blanchet S , Bouchez O , Chapman CA , Etter PD , Goldberg TL , Johnson EA , Jones JH , Loot G , Omeja PA , Rey O , Ruiz-Lopez MJ , Switzer WM , Ting N . Mol Ecol Resour 2015 15 (3) 684 This article documents the public availability of (i) transcriptome sequence data and assembly for the rostrum dace (Leuciscus burdigalensis) naturally infected by a copepod ectoparasite (Tracheliastes polycolpus) and (ii) SNPs identified and validated from RAD sequencing for the Ugandan red colobus (Procolobus rufomitratus tephrosceles) using RAD sequencing. |
Discovery and full genome characterization of a new SIV lineage infecting red-tailed guenons (Cercopithecus ascanius schmidti) in Kibale National Park, Uganda.
Lauck M , Switzer WM , Sibley SD , Hyeroba D , Tumukunde A , Weny G , Shankar A , Greene JM , Ericsen AJ , Zheng H , Ting N , Chapman CA , Friedrich TC , Goldberg TL , O'Connor DH . Retrovirology 2014 11 (1) 55 BACKGROUND: Human immunodeficiency virus (HIV) type 1 and 2, the causative agents of acquired immunodeficiency syndrome (AIDS), emerged from African non-human primates (NHPs) through zoonotic transmission of simian immunodeficiency viruses (SIV). Among African NHPs, the Cercopithecus genus contains the largest number of species known to harbor SIV. However, our understanding of the diversity and evolution of SIVs infecting this genus is limited by incomplete taxonomic and geographic sampling, particularly in East Africa. In this study, we screened blood specimens from red-tailed guenons (Cercopithecus ascanius schmidti) from Kibale National Park, Uganda, for the presence of novel SIVs using unbiased deep-sequencing. FINDINGS: We describe and characterize the first full-length SIV genomes from wild red-tailed guenons in Kibale National Park, Uganda. This new virus, tentatively named SIVrtg_Kib, was detected in five out of twelve animals and is highly divergent from other Cercopithecus SIVs as well as from previously identified SIVs infecting red-tailed guenons, thus forming a new SIV lineage. CONCLUSIONS: Our results show that the genetic diversity of SIVs infecting red-tailed guenons is greater than previously appreciated. This diversity could be the result of cross-species transmission between different guenon species or limited gene flow due to geographic separation among guenon populations. |
Discovery and full genome characterization of two highly divergent simian immunodeficiency viruses infecting black-and-white colobus monkeys (Colobus guereza) in Kibale National Park, Uganda
Lauck M , Baggett HC , Switzer WM , Sibley SD , Hyeroba D , Tumukunde A , Weny G , Taylor B , Shankar A , Ting N , Chapman CA , Friedrich TC , Goldberg TL , OConnor DH . Retrovirology 2013 10 (1) 107 BACKGROUND: African non-human primates (NHPs) are natural hosts for simian immunodeficiency viruses (SIV), the zoonotic transmission of which led to the emergence of HIV-1 and HIV-2. However, our understanding of SIV diversity and evolution is limited by incomplete taxonomic and geographic sampling of NHPs, particularly in East Africa. In this study, we screened blood specimens from nine black-and-white colobus monkeys (Colobus guereza occidentalis) from Kibale National Park, Uganda, for novel SIVs using a combination of serology and "unbiased" deep-sequencing, a method that does not rely on genetic similarity to previously characterized viruses. RESULTS: We identified two novel and divergent SIVs, tentatively named SIVkcol-1 and SIVkcol-2, and assembled genomes covering the entire coding region for each virus. SIVkcol-1 and SIVkcol-2 were detected in three and four animals, respectively, but with no animals co-infected. Phylogenetic analyses showed that SIVkcol-1 and SIVkcol-2 form a lineage with SIVcol, previously discovered in black-and-white colobus from Cameroon. Although SIVkcol-1 and SIVkcol-2 were isolated from the same host population in Uganda, SIVkcol-1 is more closely related to SIVcol than to SIVkcol-2. Analysis of functional motifs in the extracellular envelope glycoprotein (gp120) revealed that SIVkcol-2 is unique among primate lentiviruses in containing only 16 conserved cysteine residues instead of the usual 18 or more. CONCLUSIONS: Our results demonstrate that the genetic diversity of SIVs infecting black-and-white colobus across equatorial Africa is greater than previously appreciated and that divergent SIVs can co-circulate in the same colobine population. We also show that the use of "unbiased" deep sequencing for the detection of SIV has great advantages over traditional serological approaches, especially for studies of unknown or poorly characterized viruses. Finally, the detection of the first SIV containing only 16 conserved cysteines in the extracellular envelope protein gp120 further expands the range of functional motifs observed among SIVs and highlights the complex evolutionary history of simian retroviruses. |
Exceptional simian hemorrhagic fever virus diversity in a wild African primate community
Lauck M , Sibley SD , Hyeroba D , Tumukunde A , Weny G , Chapman CA , Ting N , Switzer WM , Kuhn JH , Friedrich TC , O'Connor DH , Goldberg TL . J Virol 2013 87 (1) 688-91 Simian hemorrhagic fever virus (SHFV) is an arterivirus that causes severe disease in captive macaques. We describe two new SHFV variants subclinically infecting wild African red-tailed guenons (Cercopithecus ascanius). Both variants are highly divergent from the prototype virus and variants infecting sympatric red colobus (Procolobus rufomitratus). All known SHFV variants are monophyletic and share three open reading frames not present in other arteriviruses. Our data suggest a need to modify the current arterivirus classification. |
NLRX1 protein attenuates inflammatory responses to infection by interfering with the RIG-I-MAVS and TRAF6-NF-?B signaling pathways.
Allen IC , Moore CB , Schneider M , Lei Y , Davis BK , Scull MA , Gris D , Roney KE , Zimmermann AG , Bowzard JB , Ranjan P , Monroe KM , Pickles RJ , Sambhara S , Ting JP . Immunity 2011 34 (6) 854-65 The nucleotide-binding domain and leucine-rich-repeat-containing (NLR) proteins regulate innate immunity. Although the positive regulatory impact of NLRs is clear, their inhibitory roles are not well defined. We showed that Nlrx1(-/-) mice exhibited increased expression of antiviral signaling molecules IFN-beta, STAT2, OAS1, and IL-6 after influenza virus infection. Consistent with increased inflammation, Nlrx1(-/-) mice exhibited marked morbidity and histopathology. Infection of these mice with an influenza strain that carries a mutated NS-1 protein, which normally prevents IFN induction by interaction with RNA and the intracellular RNA sensor RIG-I, further exacerbated IL-6 and type I IFN signaling. NLRX1 also weakened cytokine responses to the 2009 H1N1 pandemic influenza virus in human cells. Mechanistically, Nlrx1 deletion led to constitutive interaction of MAVS and RIG-I. Additionally, an inhibitory function is identified for NLRX1 during LPS activation of macrophages where the MAVS-RIG-I pathway was not involved. NLRX1 interacts with TRAF6 and inhibits NF-kappaB activation. Thus, NLRX1 functions as a checkpoint of overzealous inflammation. |
Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society
Harden CL , Hopp J , Ting TY , Pennell PB , French JA , Hauser WA , Wiebe S , Gronseth GS , Thurman D , Meador KJ , Koppel BS , Kaplan PW , Robinson JN , Gidal B , Hovinga CA , Wilner AN , Vazquez B , Holmes L , Krumholz A , Finnell R , Le Guen C , American Academy of Neurology American Epilepsy Society . Neurology 2009 73 (2) 126-32 OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy in WWE compared to other women, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. METHODS: A 20-member committee including general neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and February 2008. RESULTS: For WWE taking antiepileptic drugs, there is probably no substantially increased risk (greater than two times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (greater than 1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. Seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84%-92%) of remaining seizure-free during pregnancy. RECOMMENDATIONS: Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%-92%) of remaining seizure-free during pregnancy (Level B). However, WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy (Level C). |
Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society
Harden CL , Meador KJ , Pennell PB , Hauser WA , Gronseth GS , French JA , Wiebe S , Thurman D , Koppel BS , Kaplan PW , Robinson JN , Hopp J , Ting TY , Gidal B , Hovinga CA , Wilner AN , Vazquez B , Holmes L , Krumholz A , Finnell R , Hirtz D , Le Guen C , American Academy of Neurology American Epilepsy Society . Neurology 2009 73 (2) 133-41 OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy. METHODS: Systematic review of relevant articles published between January 1985 and June 2007. RESULTS: It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possible compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to monotherapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive outcomes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7. RECOMMENDATIONS: If possible, avoidance of valproate (VPA) and antiepileptic drug (AED) polytherapy during the first trimester of pregnancy should be considered to decrease the risk of major congenital malformations (Level B). If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes (Level B). If possible, avoidance of phenytoin and phenobarbital during pregnancy may be considered to prevent reduced cognitive outcomes (Level C). Pregnancy risk stratification should reflect that the offspring of women with epilepsy taking AEDs are probably at increased risk for being small for gestational age (Level B) and possibly at increased risk of 1-minute Apgar scores of <7 (Level C). |
Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society
Harden CL , Pennell PB , Koppel BS , Hovinga CA , Gidal B , Meador KJ , Hopp J , Ting TY , Hauser WA , Thurman D , Kaplan PW , Robinson JN , French JA , Wiebe S , Wilner AN , Vazquez B , Holmes L , Krumholz A , Finnell R , Shafer PO , Le Guen C , American Academy of Neurology American Epilepsy Society . Neurology 2009 73 (2) 142-9 OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy. METHODS: A 20-member committee evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and October 2007. RESULTS: Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. RECOMMENDATIONS: Supplementing women with epilepsy with at least 0.4 mg of folic acid before they become pregnant may be considered (Level C). Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered (Level B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative) levels may be considered (Level C). A paucity of evidence limited the strength of many recommendations. |
Coinfection of Ugandan red colobus (Procolobus [Piliocolobus] rufomitratus tephrosceles) with novel, divergent delta-, lenti-, and spumaretroviruses
Goldberg TL , Sintasath DM , Chapman CA , Cameron KM , Karesh WB , Tang S , Wolfe ND , Rwego IB , Ting N , Switzer WM . J Virol 2009 83 (12) 11318-29 Nonhuman primates host a plethora of potentially zoonotic microbes, with simian retroviruses receiving heightened attention due to their roles in the origin of human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2). However, incomplete taxonomic and geographic sampling of potential hosts, especially the African colobines, has left the full range of primate retrovirus diversity unexplored. Blood samples collected from 31 wild-living red colobus monkeys (Procolobus [Piliocolobus] rufomitratus tephrosceles) from Kibale National Park, Uganda, were tested for antibodies to simian immunodeficiency virus (SIV), simian T-cell lymphotrophic virus (STLV), and simian foamy virus (SFV), and for nucleic acids of these same viruses using genus-specific PCRs. Of 31 red colobus tested, 22.6% were seroreactive to SIV, 6.4% to STLV, and 97% to SFV. Phylogenetic analyses of SIV polymerase (pol), STLV tax and LTR, and SFV pol and LTR sequences revealed unique SIV and SFV strains and a novel STLV lineage, each divergent from corresponding retroviral lineages previously described in Western red colobus (P. badius badius) or black-and-white colobus (Colobus guereza). Phylogenetic analyses of host mitochondrial DNA sequences revealed that red colobus populations in East and West Africa diverged from one another approximately 4.25 million years ago. These results indicate that geographic subdivisions within the red colobus taxonomic complex exert a strong influence on retroviral phylogeny, and that studying retroviral diversity in closely related primate taxa should be particularly informative for understanding host-virus co-evolution. |
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