scholarly journals Simian Varicella Virus Infection of Rhesus Macaques Recapitulates Essential Features of Varicella Zoster Virus Infection in Humans

2009 ◽  
Vol 5 (11) ◽  
pp. e1000657 ◽  
Author(s):  
Ilhem Messaoudi ◽  
Alexander Barron ◽  
Mary Wellish ◽  
Flora Engelmann ◽  
Alfred Legasse ◽  
...  
Keyword(s):  
Virus Infection ◽  
Varicella Zoster Virus ◽  
Rhesus Macaques ◽  
Varicella Zoster Virus Infection ◽  
Simian Varicella Virus ◽  
Varicella Zoster ◽  
Varicella Virus

scholarly journals Disseminated Simian Varicella Virus Infection in an Irradiated Rhesus Macaque (Macaca mulatta)

2006 ◽  
Vol 81 (1) ◽  
pp. 411-415 ◽  
Author(s):  
Krishnan Kolappaswamy ◽  
Ravi Mahalingam ◽  
Vicki Traina-Dorge ◽  
Steven T. Shipley ◽  
Donald H. Gilden ◽  
...  
Keyword(s):  
Virus Infection ◽  
Gamma Irradiation ◽  
Varicella Zoster Virus ◽  
Macaca Mulatta ◽  
Varicella Zoster Virus Infection ◽  
Virus Reactivation ◽  
Varicella Infection ◽  
Simian Varicella Virus ◽  
Varicella Zoster ◽  
Varicella Virus

ABSTRACT 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 irradiated monkey likely led to disseminated varicella in the seronegative irradiated monkey. These findings parallel those from humans with disseminated varicella infection and support the usefulness of SVV infection as a model for human varicella-zoster virus infection, particularly virus reactivation after gamma-irradiation.

scholarly journals The ORF61 Protein Encoded by Simian Varicella Virus and Varicella-Zoster Virus Inhibits NF-κB Signaling by Interfering with IκBα Degradation

2015 ◽  
Vol 89 (17) ◽  
pp. 8687-8700 ◽  
Author(s):  
Travis Whitmer ◽  
Daniel Malouli ◽  
Luke S. Uebelhoer ◽  
Victor R. DeFilippis ◽  
Klaus Früh ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Varicella Zoster Virus ◽  
Primary Infection ◽  
Rhesus Macaques ◽  
Innate Immune ◽  
Simian Varicella Virus ◽  
Varicella Zoster ◽  
Varicella Virus

ABSTRACTVaricella-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 these inhibitory mechanismsin vivois unknown. Simian varicella virus (SVV) infection of rhesus macaques recapitulates key aspects of VZV pathogenesis, and this model thus permits examination of the role of immune evasion mechanismsin vivo. Here, we compare SVV and VZV with respect to interference with NF-κB activation. We demonstrate that both viruses prevent ubiquitination of the NF-κB inhibitor IκBα, whereas SVV additionally prevents IκBα phosphorylation. We show that the ORF61 proteins of VZV and SVV are sufficient to prevent IκBα ubiquitination upon ectopic expression. We further demonstrate that SVV ORF61 interacts with β-TrCP, a subunit of the SCF ubiquitin ligase complex that mediates the degradation of IκBα. This interaction seems to inactivate SCF-mediated protein degradation in general, since the unrelated β-TrCP target Snail is also stabilized by ORF61. In addition to ORF61, SVV seems to encode additional inhibitors of the NF-κB pathway, since SVV with ORF61 deleted still prevented IκBα phosphorylation and degradation. Taken together, our data demonstrate that SVV interferes with tumor necrosis factor alpha (TNF-α)-induced NF-κB activation at multiple levels, which is consistent with the importance of these countermechanisms for varicella virus infection.IMPORTANCEThe role of innate immunity during the establishment of primary infection, latency, and reactivation by varicella-zoster virus (VZV) is incompletely understood. Since infection of rhesus macaques by simian varicella virus (SVV) is used as an animal model of VZV infection, we characterized the molecular mechanism by which SVV interferes with innate immune activation. Specifically, we studied how SVV prevents activation of the transcription factor NF-κB, a central factor in eliciting proinflammatory responses. The identification of molecular mechanisms that counteract innate immunity might ultimately lead to better vaccines and treatments for VZV, since overcoming these mechanisms, either by small-molecule inhibition or by genetic modification of vaccine strains, is expected to reduce the pathogenic potential of VZV. Moreover, using SVV infection of rhesus macaques, it will be possible to study how increasing the vulnerability of varicella viruses to innate immunity will impact viral pathogenesis.

scholarly journals Naturally Acquired Simian Varicella Virus Infection in African Green Monkeys

2002 ◽  
Vol 76 (17) ◽  
pp. 8548-8550 ◽  
Author(s):  
Ravi Mahalingam ◽  
Vicki Traina-Dorge ◽  
Mary Wellish ◽  
John Smith ◽  
Donald H. Gilden
Keyword(s):  
Virus Infection ◽  
Dna Analysis ◽  
Experimental System ◽  
Varicella Zoster Virus Infection ◽  
Varicella Infection ◽  
Simian Varicella Virus ◽  
Varicella Zoster ◽  
Varicella Virus ◽  
Dna And Rna ◽  
Multiple Levels

ABSTRACT Simian varicella virus (SVV) infection of primates shares clinical, pathological, immunological, and virological features with varicella-zoster virus infection of humans. Natural varicella infection was simulated by exposing four SVV-seronegative monkeys to monkeys inoculated intratracheally with SVV, in which viral DNA and RNA persist in multiple tissues for more than 1 year (T. M. White, R. Mahalingam, V. Traina-Dorge, and D. H. Gilden, J. Neurovirol. 8:191-205, 2002). The four naturally exposed monkeys developed mild varicella 10 to 14 days later, and skin scrapings taken at the time of the rash contained SVV DNA. Analysis of multiple ganglia, liver, and lung tissues from the four naturally exposed monkeys sacrificed 6 to 8 weeks after resolution of the rash revealed SVV DNA in ganglia at multiple levels of the neuraxis but not in the lung or liver tissue of any of the four monkeys. This animal model provides an experimental system to gain information about varicella latency with direct relevance to the human disease.

scholarly journals Abortive Intrabronchial Infection of Rhesus Macaques with Varicella-Zoster Virus Provides Partial Protection against Simian Varicella Virus Challenge

2014 ◽  
Vol 89 (3) ◽  
pp. 1781-1793 ◽  
Author(s):  
Christine Meyer ◽  
Flora Engelmann ◽  
Nicole Arnold ◽  
David L. Krah ◽  
Jan ter Meulen ◽  
...  
Keyword(s):  
Immune Response ◽  
Herpes Zoster ◽  
Varicella Zoster Virus ◽  
Rhesus Macaques ◽  
Sensory Ganglia ◽  
Partial Protection ◽  
Simian Varicella Virus ◽  
Varicella Zoster ◽  
Varicella Virus ◽  
Cellular Immune

ABSTRACTVaricella-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, recapitulates virologic and immunologic hallmarks of VZV infection in humans. Given that VZV is acquired primarily via the respiratory route, we investigated whether intrabronchial inoculation of RMs with VZV would result in a robust model. Despite the lack of varicella and viral replication in either the lungs or whole blood, all four RMs generated an immune response characterized by the generation of VZV-specific antibodies and T cells. Two of 4 VZV-inoculated RMs were challenged with SVV to determine cross-protection. VZV-immune RMs displayed no varicella rash and had lower SVV viral loads and earlier and stronger humoral and cellular immune responses than controls. In contrast to the results for SVV DNA, no VZV DNA was detected in sensory ganglia at necropsy. In summary, following an abortive VZV infection, RMs developed an adaptive immune response that conferred partial protection against SVV challenge. These data suggest that a replication-incompetent VZV vaccine that does not establish latency may provide sufficient protection against VZV disease and that VZV vaccination of RMs followed by SVV challenge provides a model to evaluate new vaccines and therapeutics against VZV.IMPORTANCEAlthough VZV vaccine strain Oka is attenuated, it can cause mild varicella, establish latency, and in rare cases, reactivate to cause herpes zoster (HZ). Moreover, studies suggest that the HZ vaccine (Zostavax) only confers short-lived immunity. The development of more efficacious vaccines would be facilitated by a robust animal model of VZV infection. The data presented in this report show that intrabronchial inoculation of rhesus macaques (RMs) with VZV resulted in an abortive VZV infection. Nevertheless, all animals generated a humoral and cellular immune response that conferred partial cross-protection against simian varicella virus (SVV) challenge. Additionally, VZV DNA was not detected in the sensory ganglia, suggesting that viremia might be required for the establishment of latency. Therefore, VZV vaccination of RMs followed by SVV challenge is a model that will support the development of vaccines that boost protective T cell responses against VZV.

scholarly journals Intratracheal inoculation of human varicella zoster virus (VZV; MAV strain) vaccine successfully induced VZV IgG antibodies in rhesus monkeys

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Jong-Min Kim ◽  
Chung-Gyu Park
Keyword(s):  
Rhesus Monkey ◽  
Varicella Zoster Virus ◽  
Humoral Immunity ◽  
Antibody Production ◽  
Rhesus Monkeys ◽  
Igg Antibodies ◽  
Simian Varicella Virus ◽  
Varicella Zoster ◽  
Varicella Virus ◽  
Strain Vaccine

Abstract Background The objective of this study was to investigate whether the use of live attenuated varicella zoster virus (VZV) MAV vaccination can efficiently induce VZV antibody production in naive rhesus monkeys as an approach to prevent simian varicella virus (SVV) reactivation in animals immunosuppressed for transplantation studies. Results Clinically available human VZV vaccine was used to induce the production of anti-VZV antibodies in rhesus monkeys. A vial of the vaccine was subcutaneously injected at 0 week, and the second and third vaccination was performed at 5 and 6 weeks by intratracheal inoculation. The titer of anti-VZV IgG was assessed at 0, 2, 4, 6, and 7 weeks. At 2 weeks, 3/16 were seropositive for VZV IgG. At 6 weeks, 9/16 were shown to be seropositive. At 7 weeks, 16/16 were found to be seropositive. Conclusions The VZV vaccine via intratrachael inoculation was shown to induce VZV IgG humoral immunity in rhesus monkeys and may be important immunosuppressed macaques for transplantation studies. Although the humoral immunity produced is an important finding, further studies will be necessary to confirm possible protection and it could protect probably against SVV infection in rhesus monkey.

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