RESUMO
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 protein (MCP-1), interferon inducible T-cell α chemoattractant protein (I-TAC), interferon processing protein (IP-10), and anti-inflammatory interleukin-1 Receptor antagonist (IL-1Ra). After immunosuppression and at reactivation, levels of pro-inflammatory mediators MCP-1, eotaxin, IL-6, IL-8, MIF, RANTES (regulated-on-activation normal T-cell expressed and secreted), and HGF (hepatocyte growth factor) were elevated, as was the anti-inflammatory mediator IL-1Ra. Characterization of cytokine, chemokine and growth factor responses during different stages of varicella virus infection will facilitate immunotherapeutic and vaccine strategies.
Assuntos
Infecções por Herpesviridae/imunologia , Ativação Viral/imunologia , Latência Viral/imunologia , Animais , Quimiocinas/imunologia , Modelos Animais de Doenças , Inflamação/imunologia , Inflamação/virologia , Macaca mulatta , Masculino , Varicellovirus/fisiologiaRESUMO
Primary simian varicella virus (SVV) infection and reactivation in nonhuman primates is a valuable animal model in the study of varicella zoster virus disease [varicella (chickenpox) and herpes zoster (shingles)]. To understand SVV pathogenesis in skin, we inoculated 10 rhesus macaques with SVV, resulting in varicella rash. After the establishment of latency, eight of the monkeys were immunosuppressed using tacrolimus with or without irradiation and prednisone and two monkeys were not immunosuppressed. Zoster rash developed in all immunosuppressed monkeys and in one non-immunosuppressed monkey. Five monkeys had recurrent zoster. During varicella and zoster, SVV DNA in skin scrapings ranged from 50 to 107 copies/100 ng of total DNA and 2-127 copies/100 ng of total DNA, respectively. Detection of SVV DNA in blood during varicella was more frequent and abundant compared to that of zoster. During varicella and zoster, SVV antigens colocalized with neurons expressing ß-III tubulin in epidermis, hair follicles, and sweat glands, suggesting axonal transport of the virus. Together, we have demonstrated that both SVV DNA and antigens can be detected in skin lesions during varicella and zoster, providing the basis for further studies on SVV skin pathogenesis, including immune responses and mechanisms of peripheral spread.