This page has only limited features, please log in for full access.

Unclaimed
Amit Kapoor
Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43205, USA

Honors and Awards

The user has no records in this section


Career Timeline

The user has no records in this section.


Short Biography

The user biography is not available.
Following
Followers
Co Authors
The list of users this user is following is empty.
Following: 0 users

Feed

Review
Published: 12 August 2021 in Viruses
Reads 0
Downloads 0

Unless urgently needed to prevent a pandemic, the development of a viral vaccine should follow a rigorous scientific approach. Each vaccine candidate should be designed considering the in-depth knowledge of protective immunity, followed by preclinical studies to assess immunogenicity and safety, and lastly, the evaluation of selected vaccines in human clinical trials. The recently concluded first phase II clinical trial of a human hepatitis C virus (HCV) vaccine followed this approach. Still, despite promising preclinical results, it failed to protect against chronic infection, raising grave concerns about our understanding of protective immunity. This setback, combined with the lack of HCV animal models and availability of new highly effective antivirals, has fueled ongoing discussions of using a controlled human infection model (CHIM) to test new HCV vaccine candidates. Before taking on such an approach, however, we must carefully weigh all the ethical and health consequences of human infection in the absence of a complete understanding of HCV immunity and pathogenesis. We know that there are significant gaps in our knowledge of adaptive immunity necessary to prevent chronic HCV infection. This review discusses our current understanding of HCV immunity and the critical gaps that should be filled before embarking upon new HCV vaccine trials. We discuss the importance of T cells, neutralizing antibodies, and HCV genetic diversity. We address if and how the animal HCV-like viruses can be used for conceptualizing effective HCV vaccines and what we have learned so far from these HCV surrogates. Finally, we propose a logical but narrow path forward for HCV vaccine development.

ACS Style

Alex S. Hartlage; Amit Kapoor. Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up. Viruses 2021, 13, 1596 .

AMA Style

Alex S. Hartlage, Amit Kapoor. Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up. Viruses. 2021; 13 (8):1596.

Chicago/Turabian Style

Alex S. Hartlage; Amit Kapoor. 2021. "Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up." Viruses 13, no. 8: 1596.

Journal article
Published: 19 July 2021 in Sustainability
Reads 0
Downloads 0

Concern about elevated disease risk following disasters has been growing with the progression of global trends in urbanization and climate, in part because shifts in socioecological conditions can promote greater human contact with pathogen reservoirs in cities. Remarkably little is known, however, about the diversity and distributions of pathogens carried by commensal reservoirs across disaster-affected urban landscapes. To address this deficit, we characterized the assemblage structure of viruses in the serum of three widespread commensal rodents (Rattus norvegicus, Rattus rattus, and Mus musculus) that were trapped in New Orleans (LA, USA) following Hurricane Katrina. We assessed virus diversity and differentiation according to host species identity, co-occurrence and abundance, as well as prevailing landscape features known to shape urban rodent assemblages. We detected ≥34 viruses in total, including several pathogens of concern, through metagenomic analysis of serum taken from ≥149 individuals of each host species. We found that virus richness as well as assemblage composition and spatial differentiation differed by host species. Notably, we detected associations with host species co-occurrence and abundance, and while we found that assemblage structure varied by study area, we did not detect strong associations with landscape features known to influence rodent hosts. Evidence that virus diversity and assemblage structure reflect host identity more so than other factors indicates that biotic benchmarks might serve as prognostic indicators of post-disaster pathogen exposure risk in cities worldwide.

ACS Style

Anna Peterson; Himanshu Sharma; Arvind Kumar; Bruno Ghersi; Scott Emrich; Kurt Vandegrift; Amit Kapoor; Michael Blum. Rodent Virus Diversity and Differentiation across Post-Katrina New Orleans. Sustainability 2021, 13, 8034 .

AMA Style

Anna Peterson, Himanshu Sharma, Arvind Kumar, Bruno Ghersi, Scott Emrich, Kurt Vandegrift, Amit Kapoor, Michael Blum. Rodent Virus Diversity and Differentiation across Post-Katrina New Orleans. Sustainability. 2021; 13 (14):8034.

Chicago/Turabian Style

Anna Peterson; Himanshu Sharma; Arvind Kumar; Bruno Ghersi; Scott Emrich; Kurt Vandegrift; Amit Kapoor; Michael Blum. 2021. "Rodent Virus Diversity and Differentiation across Post-Katrina New Orleans." Sustainability 13, no. 14: 8034.

Research article
Published: 18 March 2021 in PLoS Pathogens
Reads 0
Downloads 0

There is an urgent need for a vaccine to prevent chronic infection by hepatitis C virus (HCV) and its many genetic variants. The first human vaccine trial, using recombinant viral vectors that stimulate pan-genotypic T cell responses against HCV non-structural proteins, failed to demonstrate efficacy despite significant preclinical promise. Understanding the factors that govern HCV T cell vaccine success is necessary for design of improved immunization strategies. Using a rat model of chronic rodent hepacivirus (RHV) infection, we assessed the impact of antigenic variation and immune escape upon success of a conceptually analogous RHV T cell vaccine. Naïve Lewis rats were vaccinated with a recombinant human adenovirus expressing RHV non-structural proteins (NS)3-5B and later challenged with a viral variant containing immune escape mutations within major histocompatibility complex (MHC) class I-restricted epitopes (escape virus). Whereas 7 of 11 (64%) rats cleared infection caused by wild-type RHV, only 3 of 12 (25%) were protected against heterologous challenge with escape virus. Uncontrolled replication of escape virus was associated with durable CD8 T cell responses targeting escaped epitopes alone. In contrast, clearance of escape virus correlated with CD4 T cell helper immunity and maintenance of CD8 T cell responses against intact viral epitopes. Interestingly, clearance of wild-type RHV infection after vaccination conferred enhanced protection against secondary challenge with escape virus. These results demonstrate that the efficacy of an RHV T cell vaccine is reduced when challenge virus contains escape mutations within MHC class I-restricted epitopes and that failure to sustain CD8 T cell responses against intact epitopes likely underlies immune failure in this setting. Further investigation of the immune responses that yield protection against diverse RHV challenges in this model may facilitate design of broadly effective HCV vaccines.

ACS Style

Alex S. Hartlage; Piyush Dravid; Christopher M. Walker; Amit Kapoor. Adenovirus-vectored T cell vaccine for hepacivirus shows reduced effectiveness against a CD8 T cell escape variant in rats. PLoS Pathogens 2021, 17, e1009391 .

AMA Style

Alex S. Hartlage, Piyush Dravid, Christopher M. Walker, Amit Kapoor. Adenovirus-vectored T cell vaccine for hepacivirus shows reduced effectiveness against a CD8 T cell escape variant in rats. PLoS Pathogens. 2021; 17 (3):e1009391.

Chicago/Turabian Style

Alex S. Hartlage; Piyush Dravid; Christopher M. Walker; Amit Kapoor. 2021. "Adenovirus-vectored T cell vaccine for hepacivirus shows reduced effectiveness against a CD8 T cell escape variant in rats." PLoS Pathogens 17, no. 3: e1009391.

Journal article
Published: 20 February 2021 in Viruses
Reads 0
Downloads 0

Human bocavirus 1 (HBoV1) has gained attention as a gene delivery vector with its ability to infect polarized human airway epithelia and 5.5 kb genome packaging capacity. Gorilla bocavirus 1 (GBoV1) VP3 shares 86% amino acid sequence identity with HBoV1 but has better transduction efficiency in several human cell types. Here, we report the capsid structure of GBoV1 determined to 2.76 Å resolution using cryo-electron microscopy (cryo-EM) and its interaction with mouse monoclonal antibodies (mAbs) and human sera. GBoV1 shares capsid surface morphologies with other parvoviruses, with a channel at the 5-fold symmetry axis, protrusions surrounding the 3-fold axis and a depression at the 2-fold axis. A 2/5-fold wall separates the 2-fold and 5-fold axes. Compared to HBoV1, differences are localized to the 3-fold protrusions. Consistently, native dot immunoblots and cryo-EM showed cross-reactivity and binding, respectively, by a 5-fold targeted HBoV1 mAb, 15C6. Surprisingly, recognition was observed for one out of three 3-fold targeted mAbs, 12C1, indicating some structural similarity at this region. In addition, GBoV1, tested against 40 human sera, showed the similar rates of seropositivity as HBoV1. Immunogenic reactivity against parvoviral vectors is a significant barrier to efficient gene delivery. This study is a step towards optimizing bocaparvovirus vectors with antibody escape properties.

ACS Style

Jennifer Yu; Mario Mietzsch; Amriti Singh; Alberto Jimenez Ybargollin; Shweta Kailasan; Paul Chipman; Nilakshee Bhattacharya; Julia Fakhiri; Dirk Grimm; Amit Kapoor; Indrė Kučinskaitė-Kodzė; Aurelija Žvirblienė; Maria Söderlund-Venermo; Robert McKenna; Mavis Agbandje-McKenna. Characterization of the GBoV1 Capsid and Its Antibody Interactions. Viruses 2021, 13, 330 .

AMA Style

Jennifer Yu, Mario Mietzsch, Amriti Singh, Alberto Jimenez Ybargollin, Shweta Kailasan, Paul Chipman, Nilakshee Bhattacharya, Julia Fakhiri, Dirk Grimm, Amit Kapoor, Indrė Kučinskaitė-Kodzė, Aurelija Žvirblienė, Maria Söderlund-Venermo, Robert McKenna, Mavis Agbandje-McKenna. Characterization of the GBoV1 Capsid and Its Antibody Interactions. Viruses. 2021; 13 (2):330.

Chicago/Turabian Style

Jennifer Yu; Mario Mietzsch; Amriti Singh; Alberto Jimenez Ybargollin; Shweta Kailasan; Paul Chipman; Nilakshee Bhattacharya; Julia Fakhiri; Dirk Grimm; Amit Kapoor; Indrė Kučinskaitė-Kodzė; Aurelija Žvirblienė; Maria Söderlund-Venermo; Robert McKenna; Mavis Agbandje-McKenna. 2021. "Characterization of the GBoV1 Capsid and Its Antibody Interactions." Viruses 13, no. 2: 330.

Journal article
Published: 01 August 2020 in Emerging Infectious Diseases
Reads 0
Downloads 0

Identifying viruses in synanthropic animals is necessary for understanding the origin of many viruses that can infect humans and developing strategies to prevent new zoonotic infections. The white-footed mouse, Peromyscus leucopus, is one of the most abundant rodent species in the northeastern United States. We characterized the serum virome of 978 free-ranging P. leucopus mice caught in Pennsylvania. We identified many new viruses belonging to 26 different virus families. Among these viruses was a highly divergent segmented flavivirus whose genetic relatives were recently identified in ticks, mosquitoes, and vertebrates, including febrile humans. This novel flavi-like segmented virus was found in rodents and shares ≤70% aa identity with known viruses in the highly conserved region of the viral polymerase. Our data will enable researchers to develop molecular reagents to further characterize this virus and its relatives infecting other hosts and to curtail their spread, if necessary.

ACS Style

Kurt J. Vandegrift; Arvind Kumar; Himanshu Sharma; Satyapramod Murthy; Laura D. Kramer; Richard Ostfeld; Peter J. Hudson; Amit Kapoor. Presence of Segmented Flavivirus Infections in North America. Emerging Infectious Diseases 2020, 26, 1810 -1817.

AMA Style

Kurt J. Vandegrift, Arvind Kumar, Himanshu Sharma, Satyapramod Murthy, Laura D. Kramer, Richard Ostfeld, Peter J. Hudson, Amit Kapoor. Presence of Segmented Flavivirus Infections in North America. Emerging Infectious Diseases. 2020; 26 (8):1810-1817.

Chicago/Turabian Style

Kurt J. Vandegrift; Arvind Kumar; Himanshu Sharma; Satyapramod Murthy; Laura D. Kramer; Richard Ostfeld; Peter J. Hudson; Amit Kapoor. 2020. "Presence of Segmented Flavivirus Infections in North America." Emerging Infectious Diseases 26, no. 8: 1810-1817.

Research article
Published: 10 July 2020 in PLOS Pathogens
Reads 0
Downloads 0

Pegiviruses frequently cause persistent infection (as defined by >6 months), but unlike most other Flaviviridae members, no apparent clinical disease. Human pegivirus (HPgV, previously GBV-C) is detectable in 1–4% of healthy individuals and another 5–13% are seropositive. Some evidence for infection of bone marrow and spleen exists. Equine pegivirus 1 (EPgV-1) is not linked to disease, whereas another pegivirus, Theiler’s disease-associated virus (TDAV), was identified in an outbreak of acute serum hepatitis (Theiler’s disease) in horses. Although no subsequent reports link TDAV to disease, any association with hepatitis has not been formally examined. Here, we characterized EPgV-1 and TDAV tropism, sequence diversity, persistence and association with liver disease in horses. Among more than 20 tissue types, we consistently detected high viral loads only in serum, bone marrow and spleen, and viral RNA replication was consistently identified in bone marrow. PBMCs and lymph nodes, but not liver, were sporadically positive. To exclude potential effects of co-infecting agents in experimental infections, we constructed full-length consensus cDNA clones; this was enabled by determination of the complete viral genomes, including a novel TDAV 3’ terminus. Clone derived RNA transcripts were used for direct intrasplenic inoculation of healthy horses. This led to productive infection detectable from week 2–3 and persisting beyond the 28 weeks of study. We did not observe any clinical signs of illness or elevation of circulating liver enzymes. The polyprotein consensus sequences did not change, suggesting that both clones were fully functional. To our knowledge, this is the first successful extrahepatic viral RNA launch and the first robust reverse genetics system for a pegivirus. In conclusion, equine pegiviruses are bone marrow tropic, cause persistent infection in horses, and are not associated with hepatitis. Based on these findings, it may be appropriate to rename the group of TDAV and related viruses as EPgV-2. Transmissible hepatitis in horses (Theiler’s disease) has been known for 100 years without knowledge of causative infectious agents. Recently, two novel equine pegiviruses (EPgV) were discovered. Whereas EPgV-1 was not associated to disease, the other was identified in an outbreak of acute serum hepatitis and therefore named Theiler’s disease-associated virus (TDAV). This finding was surprising since human and monkey pegiviruses typically cause long-term infection without associated clinical disease. Whereas no subsequent reports link TDAV to disease, the original association to hepatitis has not been formally examined. Here, we studied EPgV-1 and TDAV and found that their natural history of infection in horses were remarkably similar. Examination of various tissues identified the bone marrow as the primary site of replication for both viruses with no evidence of replication in the liver. To exclude potential effects of other infectious agents, we developed molecular full-length clones for EPgV-1 and TDAV and were able to initiate infection in horses using derived synthetic viral genetic material. This demonstrated long-term infection, but no association with hepatitis. These findings call into question the connection between TDAV, liver infection, and hepatitis in horses.

ACS Style

Joy E. Tomlinson; Raphael Wolfisberg; Ulrik Fahnøe; Himanshu Sharma; Randall W. Renshaw; Louise Nielsen; Eiko Nishiuchi; Christina Holm; Edward Dubovi; Brad R. Rosenberg; Bud C. Tennant; Jens Bukh; Amit Kapoor; Thomas J. Divers; Charles M. Rice; Gerlinde R. Van De Walle; Troels K. H. Scheel. Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis. PLOS Pathogens 2020, 16, e1008677 .

AMA Style

Joy E. Tomlinson, Raphael Wolfisberg, Ulrik Fahnøe, Himanshu Sharma, Randall W. Renshaw, Louise Nielsen, Eiko Nishiuchi, Christina Holm, Edward Dubovi, Brad R. Rosenberg, Bud C. Tennant, Jens Bukh, Amit Kapoor, Thomas J. Divers, Charles M. Rice, Gerlinde R. Van De Walle, Troels K. H. Scheel. Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis. PLOS Pathogens. 2020; 16 (7):e1008677.

Chicago/Turabian Style

Joy E. Tomlinson; Raphael Wolfisberg; Ulrik Fahnøe; Himanshu Sharma; Randall W. Renshaw; Louise Nielsen; Eiko Nishiuchi; Christina Holm; Edward Dubovi; Brad R. Rosenberg; Bud C. Tennant; Jens Bukh; Amit Kapoor; Thomas J. Divers; Charles M. Rice; Gerlinde R. Van De Walle; Troels K. H. Scheel. 2020. "Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis." PLOS Pathogens 16, no. 7: e1008677.

Journal article
Published: 04 May 2020 in Journal of Virology
Reads 0
Downloads 0

Development of vaccines against hepatitis C virus (HCV), a major cause of cirrhosis and cancer, has been stymied by a lack of animal models. The recent discovery of an HCV-like rodent hepacivirus (RHV) enabled the development of such a model in rats. This platform recapitulates HCV hepatotropism and viral chronicity necessary for vaccine testing. Currently, there are few descriptions of RHV-specific responses and why they fail to prevent persistent infection in this model. Here, we show that RHV-specific CD8 T cells, while induced early at high magnitude, do not develop into functional effectors capable of controlling virus. This defect was partially alleviated by short-term treatment with an HCV antiviral. Thus, like HCV, RHV triggers dysfunction of virus-specific CD8 T cells that are vital for infection resolution. Additional study of this evasion strategy and how to mitigate it could enhance our understanding of hepatotropic viral infections and lead to improved vaccines and therapeutics.

ACS Style

Alex S. Hartlage; Christopher M. Walker; Amit Kapoor. Priming of Antiviral CD8 T Cells without Effector Function by a Persistently Replicating Hepatitis C-Like Virus. Journal of Virology 2020, 94, 1 .

AMA Style

Alex S. Hartlage, Christopher M. Walker, Amit Kapoor. Priming of Antiviral CD8 T Cells without Effector Function by a Persistently Replicating Hepatitis C-Like Virus. Journal of Virology. 2020; 94 (10):1.

Chicago/Turabian Style

Alex S. Hartlage; Christopher M. Walker; Amit Kapoor. 2020. "Priming of Antiviral CD8 T Cells without Effector Function by a Persistently Replicating Hepatitis C-Like Virus." Journal of Virology 94, no. 10: 1.

Review
Published: 07 June 2019 in Viruses
Reads 0
Downloads 0

Ticks are vectors of several pathogens that can be transmitted to humans and their geographic ranges are expanding. The exposure of ticks to new hosts in a rapidly changing environment is likely to further increase the prevalence and diversity of tick-borne diseases. Although ticks are known to transmit bacteria and viruses, most studies of tick-borne disease have focused upon Lyme disease, which is caused by infection with Borrelia burgdorferi. Until recently, ticks were considered as the vectors of a few viruses that can infect humans and animals, such as Powassan, Tick-Borne Encephalitis and Crimean–Congo hemorrhagic fever viruses. Interestingly, however, several new studies undertaken to reveal the etiology of unknown human febrile illnesses, or to describe the virome of ticks collected in different countries, have uncovered a plethora of novel viruses in ticks. Here, we compared the virome compositions of ticks from different countries and our analysis indicates that the global tick virome is dominated by RNA viruses. Comparative phylogenetic analyses of tick viruses from these different countries reveals distinct geographical clustering of the new tick viruses. Some of these new tick RNA viruses (notably severe fever with thrombocytopenia syndrome virus and Heartland virus) were found to be associated with serious human diseases. Their relevance to public health remains unknown. It is plausible that most of these newly identified tick viruses are of endogenous origin or are restricted in their transmission potential, but the efforts to identify new tick viruses should continue. Indeed, future research aimed at defining the origin, the ecology and the spillover potential of this novel viral biodiversity will be critical to understand the relevance to public health.

ACS Style

Kurt J. Vandegrift; Amit Kapoor. The Ecology of New Constituents of the Tick Virome and Their Relevance to Public Health. Viruses 2019, 11, 529 .

AMA Style

Kurt J. Vandegrift, Amit Kapoor. The Ecology of New Constituents of the Tick Virome and Their Relevance to Public Health. Viruses. 2019; 11 (6):529.

Chicago/Turabian Style

Kurt J. Vandegrift; Amit Kapoor. 2019. "The Ecology of New Constituents of the Tick Virome and Their Relevance to Public Health." Viruses 11, no. 6: 529.

Journal article
Published: 07 March 2019 in Nature Communications
Reads 0
Downloads 0

Efforts to develop an effective vaccine against the hepatitis C virus (HCV; human hepacivirus) have been stymied by a lack of small animal models. Here, we describe an experimental rat model of chronic HCV-related hepacivirus infection and its response to T cell immunization. Immune-competent rats challenged with a rodent hepacivirus (RHV) develop chronic viremia characterized by expansion of non-functional CD8+ T cells. Single-dose vaccination with a recombinant adenovirus vector expressing hepacivirus non-structural proteins induces effective immunity in majority of rats. Resolution of infection coincides with a vigorous recall of intrahepatic cellular responses. Host selection of viral CD8 escape variants can subvert vaccine-conferred immunity. Transient depletion of CD8+ cells from vaccinated rats prolongs infection, while CD4+ cell depletion results in chronic viremia. These results provide direct evidence that co-operation between CD4+ and CD8+ T cells is important for hepacivirus immunity, and that subversion of responses can be prevented by prophylactic vaccination.

ACS Style

Alex S. Hartlage; Satyapramod Murthy; Arvind Kumar; Sheetal Trivedi; Piyush Dravid; Himanshu Sharma; Christopher M. Walker; Amit Kapoor. Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection. Nature Communications 2019, 10, 1113 .

AMA Style

Alex S. Hartlage, Satyapramod Murthy, Arvind Kumar, Sheetal Trivedi, Piyush Dravid, Himanshu Sharma, Christopher M. Walker, Amit Kapoor. Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection. Nature Communications. 2019; 10 (1):1113.

Chicago/Turabian Style

Alex S. Hartlage; Satyapramod Murthy; Arvind Kumar; Sheetal Trivedi; Piyush Dravid; Himanshu Sharma; Christopher M. Walker; Amit Kapoor. 2019. "Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection." Nature Communications 10, no. 1: 1113.

Journal article
Published: 01 February 2018 in Emerging Infectious Diseases
Reads 0
Downloads 0

Equine serum hepatitis (i.e., Theiler’s disease) is a serious and often life-threatening disease of unknown etiology that affects horses. A horse in Nebraska, USA, with serum hepatitis died 65 days after treatment with equine-origin tetanus antitoxin. We identified an unknown parvovirus in serum and liver of the dead horse and in the administered antitoxin. The equine parvovirus-hepatitis (EqPV-H) shares <50% protein identity with its phylogenetic relatives of the genus Copiparvovirus. Next, we experimentally infected 2 horses using a tetanus antitoxin contaminated with EqPV-H. Viremia developed, the horses seroconverted, and acute hepatitis developed that was confirmed by clinical, biochemical, and histopathologic testing. We also determined that EqPV-H is an endemic infection because, in a cohort of 100 clinically normal adult horses, 13 were viremic and 15 were seropositive. We identified a new virus associated with equine serum hepatitis and confirmed its pathogenicity and transmissibility through contaminated biological products.

ACS Style

Thomas J. Divers; Bud C. Tennant; Arvind Kumar; Sean McDonough; John Cullen; Nishit Bhuva; Komal Jain; Lokendra Singh Chauhan; Troels Scheel; W. Ian Lipkin; Melissa Laverack; Sheetal Trivedi; Satyapramod Srinivasa; Laurie Beard; Charles M. Rice; Peter D. Burbelo; Randall W. Renshaw; Edward Dubovi; Amit Kapoor. New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of Common Biological Product. Emerging Infectious Diseases 2018, 24, 303 -310.

AMA Style

Thomas J. Divers, Bud C. Tennant, Arvind Kumar, Sean McDonough, John Cullen, Nishit Bhuva, Komal Jain, Lokendra Singh Chauhan, Troels Scheel, W. Ian Lipkin, Melissa Laverack, Sheetal Trivedi, Satyapramod Srinivasa, Laurie Beard, Charles M. Rice, Peter D. Burbelo, Randall W. Renshaw, Edward Dubovi, Amit Kapoor. New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of Common Biological Product. Emerging Infectious Diseases. 2018; 24 (2):303-310.

Chicago/Turabian Style

Thomas J. Divers; Bud C. Tennant; Arvind Kumar; Sean McDonough; John Cullen; Nishit Bhuva; Komal Jain; Lokendra Singh Chauhan; Troels Scheel; W. Ian Lipkin; Melissa Laverack; Sheetal Trivedi; Satyapramod Srinivasa; Laurie Beard; Charles M. Rice; Peter D. Burbelo; Randall W. Renshaw; Edward Dubovi; Amit Kapoor. 2018. "New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of Common Biological Product." Emerging Infectious Diseases 24, no. 2: 303-310.

Original article
Published: 31 August 2017 in Hepatology
Reads 0
Downloads 0

The lack of a relevant, tractable, and immunocompetent animal model for hepatitis C virus (HCV) has severely impeded investigations of viral persistence, immunity, and pathogenesis. In the absence of immunocompetent models with robust HCV infection, homolog hepaciviruses in their natural host could potentially provide useful surrogate models. We isolated a rodent hepacivirus from wild rats (Rattus norvegicus), RHV‐rn1; acquired the complete viral genome sequence; and developed an infectious reverse genetics system. RHV‐rn1 resembles HCV in genomic features including the pattern of polyprotein cleavage sites and secondary structures in the viral 5′ and 3′ untranslated regions. We used site‐directed and random mutagenesis to determine that only the first of the two microRNA‐122 seed sites in the viral 5′ untranslated region is required for viral replication and persistence in rats. Next, we used the clone‐derived virus progeny to infect several inbred and outbred rat strains. Our results determined that RHV‐rn1 possesses several HCV‐defining hallmarks: hepatotropism, propensity to persist, and the ability to induce gradual liver damage. Histological examination of liver samples revealed the presence of lymphoid aggregates, parenchymal inflammation, and macrovesicular and microvesicular steatosis in chronically infected rats. Gene expression analysis demonstrated that the intrahepatic response during RHV‐rn1 infection in rats mirrors that of HCV infection, including persistent activation of interferon signaling pathways. Finally, we determined that the backbone drug of HCV direct‐acting antiviral therapy, sofosbuvir, effectively suppresses chronic RHV‐rn1 infection in rats. Conclusion: We developed RHV‐rn1‐infected rats as a fully immunocompetent and informative surrogate model to delineate the mechanisms of HCV‐related viral persistence, immunity, and pathogenesis. (Hepatology 2018).

ACS Style

Sheetal Trivedi; Satyapramod Murthy; Himanshu Sharma; Alex S. Hartlage; Arvind Kumar; Sashi V. Gadi; Peter Simmonds; Lokendra V. Chauhan; Troels K.H. Scheel; Eva Billerbeck; Peter D. Burbelo; Charles M. Rice; W. Ian Lipkin; Kurt Vandegrift; John M. Cullen; Amit Kapoor. Viral persistence, liver disease, and host response in a hepatitis C–like virus rat model. Hepatology 2017, 68, 435 -448.

AMA Style

Sheetal Trivedi, Satyapramod Murthy, Himanshu Sharma, Alex S. Hartlage, Arvind Kumar, Sashi V. Gadi, Peter Simmonds, Lokendra V. Chauhan, Troels K.H. Scheel, Eva Billerbeck, Peter D. Burbelo, Charles M. Rice, W. Ian Lipkin, Kurt Vandegrift, John M. Cullen, Amit Kapoor. Viral persistence, liver disease, and host response in a hepatitis C–like virus rat model. Hepatology. 2017; 68 (2):435-448.

Chicago/Turabian Style

Sheetal Trivedi; Satyapramod Murthy; Himanshu Sharma; Alex S. Hartlage; Arvind Kumar; Sashi V. Gadi; Peter Simmonds; Lokendra V. Chauhan; Troels K.H. Scheel; Eva Billerbeck; Peter D. Burbelo; Charles M. Rice; W. Ian Lipkin; Kurt Vandegrift; John M. Cullen; Amit Kapoor. 2017. "Viral persistence, liver disease, and host response in a hepatitis C–like virus rat model." Hepatology 68, no. 2: 435-448.

Review article
Published: 03 June 2017 in Virus Research
Reads 0
Downloads 0

Recent advances in sequencing technologies have transformed the field of virus discovery and virome analysis. Once mostly confined to the traditional Sanger sequencing based individual virus discovery, is now entirely replaced by high throughput sequencing (HTS) based virus metagenomics that can be used to characterize the nature and composition of entire viromes. To better harness the potential of HTS for the study of viromes, sample preparation methodologies use different approaches to exclude amplification of non-viral components that can overshadow low-titer viruses. These virus-sequence enrichment approaches mostly focus on the sample preparation methods, like enzymatic digestion of non-viral nucleic acids and size exclusion of non-viral constituents by column filtration, ultrafiltration or density gradient centrifugation. However, recently a new approach of virus-sequence enrichment called virome-capture sequencing, focused on the amplification or HTS library preparation stage, was developed to increase the ability of virome characterization. This new approach has the potential to further transform the field of virus discovery and virome analysis, but its technical complexity and sequence-dependence warrants further improvements. In this review we discuss the different methods, their applications and evolution, for selective sequencing based virome analysis and also propose refinements needed to harness the full potential of HTS for virome analysis.

ACS Style

Arvind Kumar; Satyapramod Murthy; Amit Kapoor. Evolution of selective-sequencing approaches for virus discovery and virome analysis. Virus Research 2017, 239, 172 -179.

AMA Style

Arvind Kumar, Satyapramod Murthy, Amit Kapoor. Evolution of selective-sequencing approaches for virus discovery and virome analysis. Virus Research. 2017; 239 ():172-179.

Chicago/Turabian Style

Arvind Kumar; Satyapramod Murthy; Amit Kapoor. 2017. "Evolution of selective-sequencing approaches for virus discovery and virome analysis." Virus Research 239, no. : 172-179.

Review
Published: 01 January 2017 in Seminars in Cell & Developmental Biology
Reads 0
Downloads 0

Worldwide, there are 185 million people infected with hepatitis C virus and approximately 350,000 people die each year from hepatitis C associated liver diseases. Human hepatitis C research has been hampered by the lack of an appropriate in vivo model system. Most of the in vivo research has been conducted on chimpanzees, which is complicated by ethical concerns, small sample sizes, high costs, and genetic heterogeneity. The house mouse system has led to greater understanding of a wide variety of human pathogens, but it is unreasonable to expect Mus musculus to be a good model system for every human pathogen. Alternative animal models can be developed in these cases. Ferrets (influenza), cotton rats (human respiratory virus), and woodchucks (hepatitis B) are all alternative models that have led to a greater understanding of human pathogens. Rodent models are tractable, genetically amenable and inbred and outbred strains can provide homogeneity in results. Recently, a rodent homolog of hepatitis C was discovered and isolated from the liver of a Peromyscus maniculatus. This represents the first small mammal (mouse) model system for human hepatitis C and it offers great potential to contribute to our understanding and ultimately aid in our efforts to combat this serious public health concern. Peromyscus are available commercially and can be used to inform questions about the origin, transmission, persistence, pathology, and rational treatment of hepatitis C. Here, we provide a disease ecologist's overview of this new virus and some suggestions for useful future experiments.

ACS Style

Kurt J. Vandegrift; Justin Critchlow; Amit Kapoor; David A. Friedman; Peter Hudson. Peromyscus as a model system for human hepatitis C: An opportunity to advance our understanding of a complex host parasite system. Seminars in Cell & Developmental Biology 2017, 61, 123 -130.

AMA Style

Kurt J. Vandegrift, Justin Critchlow, Amit Kapoor, David A. Friedman, Peter Hudson. Peromyscus as a model system for human hepatitis C: An opportunity to advance our understanding of a complex host parasite system. Seminars in Cell & Developmental Biology. 2017; 61 ():123-130.

Chicago/Turabian Style

Kurt J. Vandegrift; Justin Critchlow; Amit Kapoor; David A. Friedman; Peter Hudson. 2017. "Peromyscus as a model system for human hepatitis C: An opportunity to advance our understanding of a complex host parasite system." Seminars in Cell & Developmental Biology 61, no. : 123-130.

Review
Published: 29 September 2016 in Annual Review of Virology
Reads 0
Downloads 0

Hepaciviruses and pegiviruses constitute two closely related sister genera of the family Flaviviridae. In the past five years, the known phylogenetic diversity of the hepacivirus genera has absolutely exploded. What was once an isolated infection in humans (and possibly other primates) has now expanded to include horses, rodents, bats, colobus monkeys, cows, and, most recently, catsharks, shedding new light on the genetic diversity and host range of hepaciviruses. Interestingly, despite the identification of these many animal and primate hepaciviruses, the equine hepaciviruses remain the closest genetic relatives of the human hepaciviruses, providing an intriguing clue to the zoonotic source of hepatitis C virus. This review summarizes the significance of these studies and discusses current thinking about the origin and evolution of the animal hepaciviruses as well as their potential usage as surrogate models for the study of hepatitis C virus.

ACS Style

Alex S. Hartlage; John M. Cullen; Amit Kapoor. The Strange, Expanding World of Animal Hepaciviruses. Annual Review of Virology 2016, 3, 53 -75.

AMA Style

Alex S. Hartlage, John M. Cullen, Amit Kapoor. The Strange, Expanding World of Animal Hepaciviruses. Annual Review of Virology. 2016; 3 (1):53-75.

Chicago/Turabian Style

Alex S. Hartlage; John M. Cullen; Amit Kapoor. 2016. "The Strange, Expanding World of Animal Hepaciviruses." Annual Review of Virology 3, no. 1: 53-75.

Reference entry
Published: 15 October 2014 in eLS
Reads 0
Downloads 0
ACS Style

Amit Kapoor; W Ian Lipkin. Virus Discovery in the 21st Century. eLS 2014, 1 .

AMA Style

Amit Kapoor, W Ian Lipkin. Virus Discovery in the 21st Century. eLS. 2014; ():1.

Chicago/Turabian Style

Amit Kapoor; W Ian Lipkin. 2014. "Virus Discovery in the 21st Century." eLS , no. : 1.