The Simian varicella virus and varicella zoster virus genomes are similar in size and structure

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mentioning

confidence: 88%

mentioning

confidence: 99%

Simian Varicella Virus Expresses a Latency-Associated Transcript That Is Antisense to Open Reading Frame 61 (ICP0) mRNA in Neural Ganglia of Latently Infected Monkeys

Davis

Traina‐Dorge

et al. 2007

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“…The oligonucleotides were 29 to 39 bp in length and tiled throughout the genome every 7 to 8 bases on both forward and reverse strands. Viral DNA was isolated from nucleocapsids purified from SVV-infected Vero cells as previously described (23). Hybridization data were analyzed using SignalMap software (NimbleGen Systems, Inc., Madison, WI).…”

Section: Methodsmentioning

confidence: 99%

Attenuation of the Adaptive Immune Response in Rhesus Macaques Infected with Simian Varicella Virus Lacking Open Reading Frame 61

Meyer

Kerns

Haberthur

et al. 2013

dVaricella zoster virus (VZV) is a neurotropic alphaherpesvirus that causes chickenpox during primary infection and establishes latency in sensory ganglia. Infection of rhesus macaques (RM) with the homologous simian varicella virus (SVV) recapitulates hallmarks of VZV infection. We have shown that an antisense transcript of SVV open reading frame 61 (ORF61), a viral transactivator, was detected most frequently in latently infected RM sensory ganglia. In this study, we compared disease progression, viral replication, immune response, and the establishment of latency following intrabronchial infection with a recombinant SVV lacking ORF61 (SVV⌬ORF61) to those following infection with wild-type (WT) SVV. Varicella severity and viral latency within sensory ganglia were comparable in RMs infected with SVV⌬ORF61 and WT SVV. In contrast, viral loads, B and T cell responses, and plasma inflammatory cytokine levels were decreased in RMs infected with SVV⌬ORF61. To investigate the mechanisms underlying the reduced adaptive immune response, we compared acute SVV gene expression, frequency and proliferation of dendritic cell (DC) subsets, and the expression of innate antiviral genes in bronchoalveolar lavage (BAL) samples. The abundance of SVV transcripts in all kinetic classes was significantly decreased in RMs infected with SVV⌬ORF61. In addition, we detected a higher frequency and proliferation of plasmacytoid dendritic cells in BAL fluid at 3 days postinfection in RMs infected with SVV⌬ORF61, which was accompanied by a slight increase in type I interferon gene expression. Taken together, our data suggest that ORF61 plays an important role in orchestrating viral gene expression in vivo and interferes with the host antiviral interferon response. V aricella zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes chickenpox (varicella) during primary infection. VZV establishes a life-long latent infection in sensory ganglia, including the trigeminal and dorsal root ganglia. Reactivation of VZV leads to herpes zoster (HZ; shingles), which is estimated to affect 1 million individuals each year in the United States and can result in significant morbidity and occasionally mortality in aged and immunocompromised individuals (1-4). Reactivation of VZV is generally believed to be due to a decline in T cell immunity (5-10); however, the viral genes that control the switch between latent and lytic replication remain unknown. This is due in part to the fact that VZV is strictly a human pathogen, and animal models of VZV infection recapitulate only certain aspects of pathogenesis. We have previously shown that rhesus macaques (RMs) infected with simian varicella virus (SVV) display the hallmarks of VZV infection in humans, including generalized varicella, development of cellular and humoral immunity, and establishment of latency (11).Utilizing this model, we previously found that SVV open reading frame 61 (ORF61) was the most prevalent transcript detected during latency in sensory ganglia (12). Interestingly, SVV ORF61 ...

“…We have recently shown that intrabronchial infection of young rhesus macaques (RM) with simian varicella virus (SVV) results in disease characteristic of VZV infection in humans, with the appearance of a generalized varicella rash at 7 days postinfection (dpi), generation of T and B cell responses that peak at 7 to 14 days postinfection, resolution of viremia coincident with abatement of varicella at 21 to 35 days postinfection, and establishment of latency with limited transcriptional activity in the sensory ganglia (22,23). SVV and VZV are evolutionarily related and are colinear with respect to genome organization (24)(25)(26)(27). With a single exception (described below), each of the SVV ORFs has a corresponding VZV homolog which shares amino acid identities ranging from 75.4% (ORF31, gB) to 27.3% (ORF1), with an average 55.5% amino acid identity across the genome (26).…”

mentioning

confidence: 99%

Genome-Wide Analysis of T Cell Responses during Acute and Latent Simian Varicella Virus Infections in Rhesus Macaques

Haberthur

Kraft

Arnold

et al. 2013

f Varicella zoster virus (VZV) is the etiological agent of varicella (chickenpox) and herpes zoster (HZ [shingles]). Clinical observations suggest that VZV-specific T cell immunity plays a more critical role than humoral immunity in the prevention of VZV reactivation and development of herpes zoster. Although numerous studies have characterized T cell responses directed against select VZV open reading frames (ORFs), a comprehensive analysis of the T cell response to the entire VZV genome has not yet been conducted. We have recently shown that intrabronchial inoculation of young rhesus macaques with simian varicella virus (SVV), a homolog of VZV, recapitulates the hallmarks of acute and latent VZV infection in humans. In this study, we characterized the specificity of T cell responses during acute and latent SVV infection. Animals generated a robust and broad T cell response directed against both structural and nonstructural viral proteins during acute infection in bronchoalveolar lavage (BAL) fluid and peripheral blood. During latency, T cell responses were detected only in the BAL fluid and were lower and more restricted than those observed during acute infection. Interestingly, we identified a small set of ORFs that were immunogenic during both acute and latent infection in the BAL fluid. Given the close genome relatedness of SVV and VZV, our studies highlight immunogenic ORFs that may be further investigated as potential components of novel VZV vaccines that specifically boost T cell immunity.