| disseminated simian varicella virus infection in an irradiated rhesus macaque (macaca mulatta). | we describe correlative clinicopathological/virological findings from a simian varicella virus (svv)-seronegative monkey that developed disseminated varicella 105 days after gamma-irradiation. twelve other monkeys in the colony were also irradiated, none of which developed varicella. before irradiation, sera from the monkey that developed disseminated infection and one asymptomatic monkey were available. analysis indicated that subclinical reactivation of latent svv from an asymptomatic irradiat ... | 2007 | 17079326 |
| diagnostic exercise: papulovesicular dermatitis in rhesus macaques (macaca mulatta). | eleven rhesus monkeys developed multifocal erythematous and a vesicular rash. most recovered spontaneously, but a 21-year-old female became moribund and was euthanized. findings were of vesicular dermatitis and widespread multifocal hemorrhagic necrosis of the lungs and other viscera, with intralesional intranuclear inclusions. simian varicella virus was identified as the cause by polymerase chain reaction analysis and serologic testing. | 2008 | 18587109 |
| simian varicella virus infection of rhesus macaques recapitulates essential features of varicella zoster virus infection in humans. | simian varicella virus (svv), the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (vzv). early attempts to develop a model of vzv pathogenesis and latency in nonhuman primates (nhp) resulted in persistent infection. more recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. thus, previous nhp models were not ideally suited to analyze the immu ... | 2009 | 19911054 |
| simian varicella virus pathogenesis. | because varicella zoster virus (vzv) is an exclusively human pathogen, the development of an animal model is necessary to study pathogenesis, latency, and reactivation. the pathological, virological, and immunological features of simian varicella virus (svv) infection in nonhuman primates are similar to those of vzv infection in humans. both natural infection of cynomolgus and african green monkeys as well as intrabronchial inoculation of rhesus macaques with svv provide the most useful models t ... | 2010 | 20186611 |
| recombinant varicella vaccines induce neutralizing antibodies and cellular immune responses to siv and reduce viral loads in immunized rhesus macaques. | the development of an effective aids vaccine remains one of the highest priorities in hiv research. the live, attenuated varicella-zoster virus (vzv) oka vaccine, safe and effective for prevention of chickenpox and zoster, also has potential as a recombinant vaccine against other pathogens, including human immunodeficiency virus (hiv). the simian varicella model, utilizing simian varicella virus (svv), offers an approach to evaluate recombinant varicella vaccine candidates. recombinant svv (rsvv ... | 2010 | 20654666 |
| severe thrombocytopenia in aged rhesus macaques (macaca mulatta) infected with simian varicella virus. | simian varicella virus was diagnosed in 2 geriatric rhesus macaques (macaca mulatta). the macaques presented with typical skin lesions as well as severe thrombocytopenia as a result of infection. idiopathic thrombocytopenic purpura is a known complication of varicella zoster virus infection in humans; however, this condition has not been reported previously as a complication of svv infection. this case report discusses the clinical presentation, pathology, and thrombocytopenia of the affected ma ... | 2011 | 21333173 |
| CD4 T cell immunity is critical for the control of simian varicella virus infection in a nonhuman primate model of VZV infection. | Primary infection with varicella zoster virus (VZV) results in varicella (more commonly known as chickenpox) after which VZV establishes latency in sensory ganglia. VZV can reactivate to cause herpes zoster (shingles), a debilitating disease that affects one million individuals in the US alone annually. Current vaccines against varicella (Varivax) and herpes zoster (Zostavax) are not 100% efficacious. Specifically, studies have shown that 1 dose of varivax can lead to breakthrough varicella, alb ... | 2011 | 22102814 |
| simian varicella virus gene expression during acute and latent infection of rhesus macaques. | varicella zoster virus (vzv) is a neurotropic α-herpesvirus that causes chickenpox during primary infection and establishes latency in sensory ganglia. reactivation of vzv results in herpes zoster and other neurological complications. our understanding of the vzv transcriptome during acute and latent infection in immune competent individuals remains incomplete. infection of rhesus macaques with the homologous simian varicella virus (svv) recapitulates the hallmarks of vzv infection. we therefore ... | 2011 | 22052378 |
| robust gene expression changes in the ganglia following subclinical reactivation in rhesus macaques infected with simian varicella virus. | varicella zoster virus (vzv) causes varicella during acute infection and establishes latency in the sensory ganglia. reactivation of vzv results in herpes zoster, a debilitating and painful disease. it is believed that vzv reactivates due to a decline in cell-mediated immunity; however, the roles that cd4 versus cd8 t cells play in the prevention of herpes zoster remain poorly understood. to address this question, we used a well-characterized model of vzv infection where rhesus macaques are intr ... | 2017 | 28321697 |
| acute simian varicella virus infection causes robust and sustained changes in gene expression in the sensory ganglia. | primary infection with varicella-zoster virus (vzv), a neurotropic alphaherpesvirus, results in varicella. vzv establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. the relationship between vzv and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. intrabronchial inoculation of rhesus macaques with simian varicella virus (svv) recapitulates the hallmarks of vzv infection in human ... | 2016 | 27681124 |
| genomic and functional analysis of the host response to acute simian varicella infection in the lung. | varicella zoster virus (vzv) is the causative agent of varicella and herpes zoster. although it is well established that vzv is transmitted via the respiratory route, the host-pathogen interactions during acute vzv infection in the lungs remain poorly understood due to limited access to clinical samples. to address these gaps in our knowledge, we leveraged a nonhuman primate model of vzv infection where rhesus macaques are intrabronchially challenged with the closely related simian varicella vir ... | 2016 | 27677639 |
| cercopithecine herpesvirus 9 (simian varicella virus) infection after total-body irradiation in a rhesus macaque (macaca mulatta). | this case report describes a rhesus macaque (macaca mulatta; male; age, 5 y; weight, 6.7 kg) with anorexia, dehydration, lethargy, ataxia, and generalized skin rashes that occurred 30 d after total-body irradiation at 6.5 gy ((60)co γ-rays). physical examination revealed pale mucus membranes, a capillary refill time of 4 s, heart rate of 180 bpm. and respirations at 50 breaths per minute. diffuse multifocal maculopapulovesicular rashes were present on the body, including mucocutaneous junctions. ... | 2016 | 27053570 |
| simian varicella virus is present in macrophages, dendritic cells, and t cells in lymph nodes of rhesus macaques after experimental reactivation. | like varicella-zoster virus (vzv), simian varicella virus (svv) reactivates to produce zoster. in the present study, 5 rhesus macaques were inoculated intrabronchially with svv, and 5 months later, 4 monkeys were immunosuppressed; 1 monkey was not immunosuppressed but was subjected to the stress of transportation. in 4 monkeys, a zoster rash developed 7 to 12 weeks after immunosuppression, and a rash also developed in the monkey that was not immunosuppressed. analysis at 24 to 48 h after zoster ... | 2015 | 26178993 |
| the orf61 protein encoded by simian varicella virus and varicella-zoster virus inhibits nf-κb signaling by interfering with iκbα degradation. | varicella-zoster virus (vzv) causes chickenpox upon primary infection and establishes latency in ganglia. reactivation from latency causes herpes zoster, which may be complicated by postherpetic neuralgia. innate immunity mediated by interferon and proinflammatory cytokines represents the first line of immune defense upon infection and reactivation. vzv is known to interfere with multiple innate immune signaling pathways, including the central transcription factor nf-κb. however, the role of the ... | 2015 | 26085158 |
| varicella viruses inhibit interferon-stimulated jak-stat signaling through multiple mechanisms. | varicella zoster virus (vzv) causes chickenpox in humans and, subsequently, establishes latency in the sensory ganglia from where it reactivates to cause herpes zoster. infection of rhesus macaques with simian varicella virus (svv) recapitulates vzv pathogenesis in humans thus representing a suitable animal model for vzv infection. while the type i interferon (ifn) response has been shown to affect vzv replication, the virus employs counter mechanisms to prevent the induction of anti-viral ifn s ... | 2015 | 25973608 |
| impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques. | in this study we examined the effects of non-myeloablative total body irradiation (tbi) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. our results show that the administration of cyclosporin a or tacrolimus without radiotherapy did not result in lymphopenia. the addition of tbi to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. dendritic cell (dc) numbers in whol ... | 2015 | 25902927 |
| abortive intrabronchial infection of rhesus macaques with varicella-zoster virus provides partial protection against simian varicella virus challenge. | varicella-zoster virus (vzv) is a human neurotropic alphaherpesvirus and the etiological agent of varicella (chickenpox) and herpes zoster (hz, shingles). previously, inoculation of monkeys via the subcutaneous, intratracheal, intravenous, or oral-nasal-conjunctival routes did not recapitulate all the hallmarks of vzv infection, including varicella, immunity, latency, and reactivation. intrabronchial inoculation of rhesus macaques (rms) with simian varicella virus (svv), a homolog of vzv, recapi ... | 2015 | 25410871 |
| intrabronchial infection of rhesus macaques with simian varicella virus results in a robust immune response in the lungs. | varicella-zoster virus (vzv) is the etiological agent of varicella (chickenpox) and herpes zoster (shingles). primary vzv infection is believed to occur via the inhalation of virus either in respiratory droplets or from shedding varicella lesions or by direct contact with infectious vesicular fluid. however, the ensuing immune response in the lungs remains incompletely understood. we have shown that intrabronchial inoculation of rhesus macaques with simian varicella virus (svv), a homolog of vzv ... | 2014 | 25142604 |
| robust pro-inflammatory and lesser anti-inflammatory immune responses during primary simian varicella virus infection and reactivation in rhesus macaques. | simian varicella virus (svv) infection of non-human primates models human varicella zoster virus (vzv) infection. assessment of cell signaling immune responses in monkeys after primary svv infection, after immunosuppression and during reactivation revealed strong pro-inflammatory responses and lesser anti-inflammatory components during varicella and reactivation. pro-inflammatory mediators elevated during varicella included interferon-gamma (ifn-γ), interleukin (il)-6, monocyte chemoattractant p ... | 2014 | 25139181 |
| t cells increase before zoster and pd-1 expression increases at the time of zoster in immunosuppressed nonhuman primates latently infected with simian varicella virus. | like varicella zoster virus in humans, simian varicella virus (svv) becomes latent in ganglionic neurons along the entire neuraxis and reactivates in immunosuppressed monkeys. five rhesus macaques were inoculated with svv; 142 days later (latency), four monkeys were immunosuppressed, and t cells were analyzed for naïve, memory, and effector phenotypes and expression of programmed death receptor-1 (pd-1; t cell exhaustion). all t cell subsets decreased during immunosuppression and except for cd8 ... | 2014 | 24549971 |
| bacterial artificial chromosome derived simian varicella virus is pathogenic in vivo. | varicella zoster virus (vzv) is a neurotropic alphaherpesvirus that infects humans and results in chickenpox and herpes zoster. a number of vzv genes remain functionally uncharacterized and since vzv is an obligate human pathogen, rigorous evaluation of vzv mutants in vivo remains challenging. simian varicella virus (svv) is homologous to vzv and svv infection of rhesus macaques (rm) closely mimics vzv infection of humans. recently the svv genome was cloned as a bacterial artificial chromosome ( ... | 2013 | 24010815 |
| genome-wide analysis of t cell responses during acute and latent simian varicella virus infections in rhesus macaques. | 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 y ... | 2013 | 23986583 |
| age and immune status of rhesus macaques impact simian varicella virus gene expression in sensory ganglia. | simian varicella virus (svv) infection of rhesus macaques (rms) recapitulates the hallmarks of varicella-zoster virus (vzv) infection of humans, including the establishment of latency within the sensory ganglia. various factors, including age and immune fitness, influence the outcome of primary vzv infection, as well as reactivation resulting in herpes zoster (hz). to increase our understanding of the role of lymphocyte subsets in the establishment of viral latency, we analyzed the latent svv tr ... | 2013 | 23698305 |
| attenuation of the adaptive immune response in rhesus macaques infected with simian varicella virus lacking open reading frame 61. | varicella 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 progressio ... | 2013 | 23221560 |
| increased cellular immune responses and cd4+ t-cell proliferation correlate with reduced plasma viral load in siv challenged recombinant simian varicella virus - simian immunodeficiency virus (rsvv-siv) vaccinated rhesus macaques. | an effective aids vaccine remains one of the highest priorities in hiv-research. our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rsvv) vector - simian immunodeficiency virus (siv) envelope and gag genes, induced neutralizing antibodies and cellular immune responses to siv and also significantly reduced plasma viral loads following intravenous pathogenic challenge with sivmac251/cx1. | 2012 | 22889373 |
| simian varicella virus infection of chinese rhesus macaques produces ganglionic infection in the absence of rash. | varicella-zoster virus (vzv) causes varicella (chickenpox), becomes latent in ganglia along the entire neuraxis, and may reactivate to cause herpes zoster (shingles). vzv may infect ganglia via retrograde axonal transport from infected skin or through hematogenous spread. simian varicella virus (svv) infection of rhesus macaques provides a useful model system to study the pathogenesis of human vzv infection. to dissect the virus and host immune factors during acute svv infection, we analyzed fou ... | 2012 | 22399159 |
| simian varicella virus causes robust transcriptional changes in t cells that support viral replication. | varicella zoster virus (vzv) causes varicella (chickenpox) during acute infection. several studies have shown that t cells are early and preferential targets of vzv infection that play a critical role in disseminating vzv in to the skin and ganglia. however, the transcriptional changes that occur in vzv-infected t cells remain unclear due to limited access to clinical samples and robust translational animal models. in this study, we used a nonhuman primate model of vzv infection where rhesus mac ... | 2017 | 28698046 |
| attenuation of simian varicella virus infection by enhanced green fluorescent protein in rhesus macaques. | simian varicella virus (svv), the primate counterpart of varicella zoster virus, causes varicella (chickenpox), establishes latency in ganglia and reactivates to produce zoster. we previously demonstrated that a recombinant svv expressing the enhanced green fluorescent protein (rsvv.egfp) is slightly attenuated both in culture and infected monkeys. herein, we generated two additional recombinant svvs to visualize infected cells in vitro and in vivo one harbors egfp fused to the n-terminus of ope ... | 2018 | 29343566 |
| elevated serum substance p during simian varicella virus infection in rhesus macaques: implications for chronic inflammation and adverse cerebrovascular events. | varicella and zoster, produced by varicella-zoster virus (vzv), are associated with an increased risk of stroke that may be due to persistent inflammation and hypercoagulability. because substance p is associated with inflammation, hypercoagulability, and atherosclerotic plaque rupture that may contribute to increased stroke risk after vzv infection, we measured serum substance p in simian varicella virus-infected rhesus macaques. we found significantly increased and persistent serum substance p ... | 2020 | 32964407 |
| current in vivo models of varicella-zoster virus neurotropism. | varicella-zoster virus (vzv), an exclusively human herpesvirus, causes chickenpox and establishes a latent infection in ganglia, reactivating decades later to produce zoster and associated neurological complications. an understanding of vzv neurotropism in humans has long been hampered by the lack of an adequate animal model. for example, experimental inoculation of vzv in small animals including guinea pigs and cotton rats results in the infection of ganglia but not a rash. the severe combined ... | 2019 | 31159224 |
| simian varicella virus dna in saliva and buccal cells after experimental acute infection in rhesus macaques. | simian varicella virus (svv) infection of non-human primates is the counterpart of varicella zoster virus (vzv) infection in humans. to develop non-invasive methods of assessing svv infection, we tested for the presence of svv dna in saliva, as has been documented in human vzv infection, and in buccal cells to determine whether epithelial cells might provide a more reliable source of material for analysis. five rhesus macaques intratracheally inoculated with svv all developed varicella with vire ... | 2019 | 31143167 |
| varicella virus-host interactions during latency and reactivation: lessons from simian varicella virus. | varicella zoster virus (vzv) is a neurotropic alphaherpesvirus and the causative agent of varicella (chickenpox) in humans. following primary infection, vzv establishes latency in the sensory ganglia and can reactivate to cause herpes zoster, more commonly known as shingles, which causes significant morbidity, and on rare occasions mortality, in the elderly. because vzv infection is highly restricted to humans, the development of a reliable animal model has been challenging, and our understandin ... | 2018 | 30619226 |
| reactivation of simian varicella virus in rhesus macaques after cd4 t cell depletion. | rhesus macaques intrabronchially inoculated with simian varicella virus (svv), the counterpart of human varicella-zoster virus (vzv), developed primary infection with viremia and rash, which resolved upon clearance of viremia, followed by the establishment of latency. to assess the role of cd4 t cell immunity in reactivation, monkeys were treated with a single 50-mg/kg dose of a humanized monoclonal anti-cd4 antibody; within 1 week, circulating cd4 t cells were reduced from 40 to 60% to 5 to 30% ... | 2019 | 30404798 |
| long-term safety outcome of systemic immunosuppression in pig-to-nonhuman primate corneal xenotransplantation. | safety concerns exist for corneal recipients under immunosuppression. we report long-term safety results of porcine corneal xenotransplantation under immunosuppression in nonhuman primates. | 2018 | 30264877 |