Pathogenesis of simian varicella virus

Abstract

Simian varicella virus (SVV) is closely related to varicella-zoster virus (VZV) and induces a natural varicella-like disease in nonhuman primates. Therefore, simian varicella is a useful model to investigate varicella pathogenesis and to evaluate antiviral therapies. In this report, we review recent studies on SVV pathogenesis and latency. Experimental infection of African green monkeys is followed by a 7-10 day incubation period during which a viremia disseminates the virus throughout the body. Clinical disease is characterized by fever and vesicular skin rash. Pneumonia and hepatitis may occur during more severe infections. Examination of acutely infected tissues reveals histopathology including necrosis and hemorrhage in the skin, lung, liver, and spleen. In contrast, the neural ganglia exhibit minimal histopathology. SVV DNA, immediate early, early, and late gene transcripts, and viral antigens are detected in the tissues of acutely infected monkeys. Host immune responses are induced which resolve the acute infection within 21 days. During or after acute infection, SVV establishes latent infection in the ganglia of surviving monkeys. The virus may reactivate later in life to cause secondary disease and viral transmission to susceptible monkeys.

Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Human Varicella-Zoster Virus

“…A second, more pronounced viremia occurs between 10 and 21 days after infection. Infection of susceptible nonhuman primates, such as African green monkeys with simian varicella virus (SVV), induces a transient viremia peaking 7 to 10 days following experimental intratracheal inoculation (12). As such, we focused our attempts to detect virus within the first 28 days following experimental inoculation by assessing both mucosal and systemic sites.…”

CD4 T Cell Immunity Is Critical for the Control of Simian Varicella Virus Infection in a Nonhuman Primate Model of VZV Infection

“…Simian varicella virus (SVV) is a neurotropic alphaherpesvirus that naturally infects non-human primates (NHP) and shares 75% DNA homology and genome colinearity with VZV [41], [42], [43]. The exact mode of SVV transmission has not yet been experimentally determined but it is believed to occur through contact with skin lesions of an infected animal, or via exposure to virus-laden aerosolized droplets from infected animal(s), as described for VZV transmission in humans [44], [45]. We have recently shown that intrabronchial infection of rhesus macaques (RM) with SVV recapitulates the hallmarks of acute VZV infection in humans: (1) generalized varicella rash; (2) development of cellular and humoral responses; (3) resolution of acute infection; and (4) establishment of latency in sensory ganglia [46].…”

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

“…The pathogenesis and clinical features of simian and human varicella are comparable (13,20). Following resolution of primary disease, SVV and VZV establish latent infections within neurons of the neural ganglia and may subsequently reactivate to cause a secondary disease, such as herpes zoster (13,22,26,30).…”