Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-10 (of 10 Records) |
Query Trace: Burgado J [original query] |
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New methylene blue derivatives suggest novel anti-orthopoxviral strategies
Priyamvada L , Burgado J , Baker-Wagner M , Kitaygorodskyy A , Olson V , Lingappa VR , Satheshkumar PS . Antiviral Res 2021 191 105086 Decades after the eradication of smallpox and the discontinuation of routine smallpox vaccination, over half of the world's population is immunologically naïve to variola virus and other orthopoxviruses (OPXVs). Even in those previously vaccinated against smallpox, protective immunity wanes over time. As such, there is a concomitant increase in the incidence of human OPXV infections worldwide. To identify novel antiviral compounds with potent anti-OPXV potential, we characterized the inhibitory activity of PAV-866 and other methylene blue derivatives against the prototypic poxvirus, vaccinia virus (VACV). These compounds inactivated virions prior to infection and consequently inhibited viral binding, fusion and entry. The compounds exhibited strong virucidal activity at non-cytotoxic concentrations, and inhibited VACV infection when added before, during or after viral adsorption. The compounds were effective against other OPXVs including monkeypox virus, cowpox virus and the newly identified Akhmeta virus. Altogether, these findings reveal a novel mode of inhibition that has not previously been demonstrated for small molecule compounds against VACV. Additional studies are in progress to determine the in vivo efficacy of these compounds against OPXVs and further characterize the anti-viral effects of these derivatives. |
Progressive vaccinia acquired through zoonotic transmission in a patient with HIV/AIDS, Colombia
Laiton-Donato K , Avila-Robayo P , Paez-Martinez A , Benjumea-Nieto P , Usme-Ciro JA , Pinzon-Narino N , Giraldo I , Torres-Castellanos D , Nakazawa Y , Patel N , Wilkins K , Li Y , Davidson W , Burgado J , Satheshkumar PS , Styczynski A , Mauldin MR , Gracia-Romero M , Petersen BW . Emerg Infect Dis 2020 26 (3) 601-605 In March 2015, a patient in Colombia with HIV/AIDS was hospitalized for disseminated ulcers after milking cows that had vesicular lesions on their udders. Vaccinia virus was detected, and the case met criteria for progressive vaccinia acquired by zoonotic transmission. Adherence to an optimized antiretroviral regimen resulted in recovery. |
Seroprevalence and risk factors possibly associated with emerging zoonotic vaccinia virus in a farming community, Colombia
Styczynski A , Burgado J , Walteros D , Usme-Ciro J , Laiton K , Farias AP , Nakazawa Y , Chapman C , Davidson W , Mauldin M , Morgan C , Martinez-Ceron J , Patina E , Lopez Sepulveda LL , Torres CP , Cruz Suarez AE , Olaya GP , Riveros CE , Cepeda DY , Lopez LA , Espinosa DG , Gutierrez Lozada FA , Li Y , Satheshkumar PS , Reynolds M , Gracia-Romero M , Petersen B . Emerg Infect Dis 2019 25 (12) 2169-76 In 2014, vaccinia virus (VACV) infections were identified among farmworkers in Caqueta Department, Colombia; additional cases were identified in Cundinamarca Department in 2015. VACV, an orthopoxvirus (OPXV) used in the smallpox vaccine, has caused sporadic bovine and human outbreaks in countries such as Brazil and India. In response to the emergence of this disease in Colombia, we surveyed and collected blood from 134 farmworkers and household members from 56 farms in Cundinamarca Department. We tested serum samples for OPXV antibodies and correlated risk factors with seropositivity by using multivariate analyses. Fifty-two percent of farmworkers had OPXV antibodies; this percentage decreased to 31% when we excluded persons who would have been eligible for smallpox vaccination. The major risk factors for seropositivity were municipality, age, smallpox vaccination scar, duration of time working on a farm, and animals having vaccinia-like lesions. This investigation provides evidence for possible emergence of VACV as a zoonosis in South America. |
Asymptomatic orthopoxvirus circulation in humans in the wake of a monkeypox outbreak among chimpanzees in Cameroon
Guagliardo SAJ , Monroe B , Moundjoa C , Athanase A , Okpu G , Burgado J , Townsend MB , Satheshkumar PS , Epperson S , Doty JB , Reynolds MG , Dibongue EE , Etoundi GA , Mathieu E , McCollum AM . Am J Trop Med Hyg 2019 102 (1) 206-212 Monkeypox virus is a zoonotic Orthopoxvirus (OPXV) that causes smallpox-like illness in humans. In Cameroon, human monkeypox cases were confirmed in 2018, and outbreaks in captive chimpanzees occurred in 2014 and 2016. We investigated the OPXV serological status among staff at a primate sanctuary (where the 2016 chimpanzee outbreak occurred) and residents from nearby villages, and describe contact with possible monkeypox reservoirs. We focused specifically on Gambian rats (Cricetomys spp.) because it is a recognized possible reservoir and because contact with this species was common enough to render sufficient statistical power. We collected one 5-mL whole blood specimen from each participant to perform a generic anti-OPXV ELISA test for IgG and IgM antibodies and administered a questionnaire about prior symptoms of monkeypox-like illness and contact with possible reservoirs. Our results showed evidence of OPXV exposures (IgG positive, 6.3%; IgM positive, 1.6%) among some of those too young to have received smallpox vaccination (born after 1980, n = 63). No participants reported prior symptoms consistent with monkeypox. After adjusting for the education level, participants who frequently visited the forest were more likely to have recently eaten Gambian rats (OR: 3.36, 95% CI: 1.91-5.92, P < 0.001) and primate sanctuary staff were less likely to have touched or sold Gambian rats (OR: 0.23, 95% CI: 0.19-0.28, P < 0.001). The asymptomatic or undetected circulation of OPXVs in humans in Cameroon is likely, and contact with monkeypox reservoirs is common, raising the need for continued surveillance for human and animal disease. |
Preemptive tecovirimat use in an active duty member presenting with acute myeloid leukemia after smallpox vaccination
Lindholm DA , Fisher RD , Montgomery JR , Davidson W , Yu PA , Yu YC , Burgado J , Wilkins K , Petersen BW , Okulicz JF . Clin Infect Dis 2019 69 (12) 2205-2207 Smallpox vaccine is contraindicated in immunosuppression due to increased risk for adverse reactions (e.g., progressive vaccinia). We describe the first-ever use of tecovirimat as a preemptive vaccinia virus treatment strategy during induction chemotherapy in an active duty member who presented with acute leukemia and inadvertent auto-inoculation after smallpox vaccination. |
Epidemiologic and ecologic investigations of monkeypox, Likouala Department, Republic of the Congo, 2017
Doshi RH , Guagliardo SAJ , Doty JB , Babeaux AD , Matheny A , Burgado J , Townsend MB , Morgan CN , Satheshkumar PS , Ndakala N , Kanjingankolo T , Kitembo L , Malekani J , Kalemba L , Pukuta E , N'Kaya T , Kangoula F , Moses C , McCollum AM , Reynolds MG , Mombouli JV , Nakazawa Y , Petersen BW . Emerg Infect Dis 2019 25 (2) 281-289 Monkeypox, caused by a zoonotic orthopoxvirus, is endemic in Central and West Africa. Monkeypox has been sporadically reported in the Republic of the Congo. During March 22-April 5, 2017, we investigated 43 suspected human monkeypox cases. We interviewed suspected case-patients and collected dried blood strips and vesicular and crust specimens (active lesions), which we tested for orthopoxvirus antibodies by ELISA and monkeypox virus and varicella zoster virus DNA by PCR. An ecologic investigation was conducted around Manfouete, and specimens from 105 small mammals were tested for anti-orthopoxvirus antibodies or DNA. Among the suspected human cases, 22 met the confirmed, probable, and possible case definitions. Only 18 patients had available dried blood strips; 100% were IgG positive, and 88.9% (16/18) were IgM positive. Among animals, only specimens from Cricetomys giant pouched rats showed presence of orthopoxvirus antibodies, adding evidence to this species' involvement in the transmission and maintenance of monkeypox virus in nature. |
A high throughput neutralization test based on GFP expression by recombinant rabies virus
Burgado J , Greenberg L , Niezgoda M , Kumar A , Olson V , Wu X , Satheshkumar PS . PLoS Negl Trop Dis 2018 12 (12) e0007011 The effectiveness of rabies vaccination in both humans and animals is determined by the presence of virus neutralizing antibodies (VNAs). The Rapid Fluorescent Focus Inhibition Test (RFFIT) is the method traditionally used for detection and quantification of VNAs. It is a functional in vitro test for assessing the ability of antibodies in serum to bind and prevent infection of cultured cells with rabies virus (RABV). The RFFIT is a labor intensive, low throughput and semi-quantitative assay performed by trained laboratorians. It requires staining of RABV-infected cells by rabies specific fluorescent antibodies and manual quantification of fluorescent fields for titer determination. Although the quantification of fluorescent fields observed in each sample is recorded, the corresponding images are not stored or captured to be used for future analysis. To circumvent several of these disadvantages, we have developed an alternative, automated high throughput neutralization test (HTNT) for determination of rabies VNAs based on green fluorescent protein (GFP) expression by a recombinant RABV and compared with the RFFIT. The HTNT assay utilizes the recombinant RABV ERA variant expressing GFP with a nuclear localization signal (NLS) for efficient quantification. The HTNT is a quantitative method where the number of RABV-infected cells are determined and the images are stored for future analysis. Both RFFIT and HTNT results correlated 100% for a panel of human and animal positive and negative rabies serum samples. Although, the VNA titer values are generally agreeable, HTNT titers tend to be lower than that of RFFIT, probably due to the differences in quantification methods. Our data demonstrates the potential for HTNT assays in determination of rabies VNA titers. |
Isolation and identification of compounds from Kalanchoe pinnata having human alphaherpesvirus and vaccinia virus antiviral activity
Cryer M , Lane K , Greer M , Cates R , Burt S , Andrus M , Zou J , Rogers P , Hansen MD , Burgado J , Panayampalli SS , Day CW , Smee DF , Johnson BF . Pharm Biol 2017 55 (1) 1586-1591 CONTEXT: Kalanchoe pinnata (Lam.) Pers. (Crassulaceae) is a succulent plant that is known for its traditional antivirus and antibacterial usage. OBJECTIVE: This work examines two compounds identified from the K. pinnata plant for their antivirus activity against human alphaherpesvirus (HHV) 1 and 2 and vaccinia virus (VACV). MATERIALS AND METHODS: Compounds KPB-100 and KPB-200 were isolated using HPLC and were identified using NMR and MS. Both compounds were tested in plaque reduction assay of HHV-2 wild type (WT) and VACV. Both compounds were then tested in virus spread inhibition and virus yield reduction (VYR) assays of VACV. KPB-100 was further tested in viral cytopathic effect (CPE) inhibition assay of HHV-2 TK-mutant and VYR assay of HHV-1 WT. RESULTS: KPB-100 and KPB-200 inhibited HHV-2 at IC50 values of 2.5 and 2.9 mug/mL, respectively, and VACV at IC50 values of 3.1 and 7.4 mug/mL, respectively, in plaque reduction assays. In virus spread inhibition assay of VACV KPB-100 and KPB-200 yielded IC50 values of 1.63 and 13.2 mug/mL, respectively, and KPB-100 showed a nearly 2-log reduction in virus in VYR assay of VACV at 20 mug/mL. Finally, KPB-100 inhibited HHV-2 TK- at an IC50 value of 4.5 mug/mL in CPE inhibition assay and HHV-1 at an IC90 of 3.0 mug/mL in VYR assay. DISCUSSION AND CONCLUSION: Both compounds are promising targets for synthetic optimization and in vivo study. KPB-100 in particular showed strong inhibition of all viruses tested. |
Monkeypox virus host factor screen in haploid cells identifies essential role of GARP complex in extracellular virus formation.
Realegeno S , Puschnik AS , Kumar A , Goldsmith C , Burgado J , Sambhara S , Olson VA , Carroll D , Damon I , Hirata T , Kinoshita T , Carette JE , Satheshkumar PS . J Virol 2017 91 (11) Monkeypox virus (MPXV) is a human pathogen that is a member of the Orthopoxvirus genus, which includes Vaccinia virus and Variola virus (the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. The screen revealed several candidate genes, including those involved in Golgi trafficking, glycosaminoglycan biosynthesis and glycosylphosphatidylinositol (GPI) - anchor biosynthesis. We validated the role of a set of vacuolar protein sorting (VPS) genes during infection, VPS51-54, which comprise the Golgi-associated retrograde protein (GARP) complex. The GARP complex is a tethering complex involved in retrograde transport of endosomes to the trans-Golgi apparatus. Our data demonstrate that VPS52 and VPS54 were dispensable for mature virus (MV) production but were required for extracellular virus (EV) formation. For comparison, a known antiviral compound, ST-246, was used in our experiments demonstrating that EV titers in VPS52 and VPS54 knockout (KO) cells were comparable to levels exhibited by ST-246 treated wildtype cells. Confocal microscopy was used to examine actin tail formation, one of the viral egress mechanisms for cell-to-cell dissemination, and revealed an absence of actin tails in VPS52KO or VPS54KO infected cells. Further evaluation of these cells by electron microscopy demonstrated a decrease in wrapped viruses (WV) compared to wild type control. Collectively, our data demonstrate the role of GARP complex genes in double-membrane wrapping of MV necessary for EV formation, implicating the host endosomal trafficking pathway in orthopoxvirus infection.IMPORTANCE Human monkeypox is an emerging zoonotic infectious disease caused by Monkeypox virus (MPXV). Of the two MPXV clades, the Congo Basin strain is associated with severe disease, higher mortality, and increased human-to-human transmission relative to the West African strain. Monkeypox is endemic to regions of western and central Africa but was introduced into the United States in 2003 from the importation of infected animals. The threat of MPXV and other orthopoxviruses is increasing due to the absence of routine smallpox vaccination leading to a higher proportion of naive populations. In this study, we have identified and validated candidate genes that are required for MPXV infection, specifically the Golgi-associated retrograde protein (GARP) complex. Identifying host targets required for infection that prevents extracellular virus formation such as the GARP complex or the retrograde pathway can provide a potential target for anti-viral therapy. |
Novel orthopoxvirus infection in an Alaska resident
Springer YP , Hsu CH , Werle ZR , Olson LE , Cooper MP , Castrodale LJ , Fowler N , McCollum AM , Goldsmith CS , Emerson GL , Wilkins K , Doty JB , Burgado J , Gao J , Patel N , Mauldin MR , Reynolds MG , Satheshkumar PS , Davidson W , Li Y , McLaughlin JB . Clin Infect Dis 2017 64 (12) 1737-1741 Background: Human infection by orthopoxviruses is being reported with increasing frequency, attributed in part to the cessation of smallpox vaccination and concomitant waning of population-level immunity. In July 2015, a female resident of interior Alaska, presented to an urgent care clinic with a dermal lesion consistent with poxvirus infection. Laboratory testing of a virus isolated from the lesion confirmed infection by an Orthopoxvirus. Methods: The virus isolate was characterized by using electron microscopy and nucleic acid sequencing. An epidemiologic investigation that included patient interviews, contact tracing and serum testing, as well as environmental and small mammal sampling was conducted to identify the infection source and possible additional cases. Results: Neither signs of active infection nor evidence of recent prior infection were observed in any of the 4 patient contacts identified. The patient's infection source was not definitively identified. Potential routes of exposure included imported fomites from Azerbaijan by the patient's cohabiting partner, or from wild small mammals in or around the patient's residence. Phylogenetic analyses demonstrated that the virus represents a distinct and previously undescribed genetic lineage of Orthopoxvirus, which is most closely related to the Old World orthopoxviruses. Conclusions: Investigation findings point to infection of the patient following exposure in or near Fairbanks. This conclusion raises questions about the geographic origins (Old World versus North American) of the genus Orthopoxvirus. Clinicians should remain vigilant for signs of poxvirus infection and alert public health officials when cases are suspected. |
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