Varicella virus-mononuclear cell interaction.

Varicella zoster virus (VZV) causes varicella (chickenpox), becomes latent in cranial nerve, dorsal root, and autonomic ganglia; and reactivates decades later to produce zoster (shingles). The main complication of zoster is postherpetic neuralgia (PHN), pain that persists for months and often years after zoster. VZV also causes chronic radicular pain without rash (zoster sine herpete). Viremia is associated with each stage of VZV infection. Viral DNA has been found in peripheral blood mononuclear cells (MNCs) of patients with varicella, zoster, PHN, and zoster sine herpete. In varicella, viremia contributes to the widespread distribution of skin lesions and infection of multiple organs. Although the role of viremia in other VZV-associated diseases is not as clear, the detection of VZV DNA (and sometimes VZV RNA and proteins) helps diagnose neurological diseases produced by VZV, has indicated that PHN may reflect a chronic VZV ganglionitis, and has established that VZV reactivates subclinically, especially in immunocompromised humans. In vitro studies have established that VZV can productively infect MNCs for a short time and have identified the subpopulations of MNCs that are infected. Finally, simian varicella virus (SVV) infection of nonhuman primates shares clinical, pathological, and virologic features with VZV in humans. Like VZV, SV viremia in nonhuman primates during acute infection plays an important role in the pathogenesis of SVV. Infectious virus can be isolated from MNCs, and SVV DNA can be detected in MNCs during varicella. Further, SVV DNA can be detected for months in MNCs of monkeys after experimental infection with SVV. Herein, we review the current literature related to VZV infection of MNCs during naturally occurring varicella, PHN, and zoster sine herpete in humans, including studies of experimental infection of human MNCs with VZV. We also review SVV MNC interaction during naturally occurring simian varicella and after experimental infection of primates with SVV.

Simian varicella virus DNA is present and transcribed months after experimental infection of adult African green monkeys.

To study the pathogenesis of simian varicella virus (SVV) infection in its natural primate host, we inoculated adult SVV-seronegative African green monkeys intratracheally with 10(3)-10(4) PFU of SVV, sacrificed them 11 days, 2, 5, 10, and 12 months postinfection (p.i.), and examined lung, liver, and ganglia for SVV DNA and RNA. PCR analysis revealed SVV DNA in ganglia and viscera at 11 days and 2, 5, and 10 months p.i. Similarly, SVV transcripts corresponding to immediate early (IE), putative early (E), and late (L) SVV open-reading frames (ORFs) were found in liver, lung, and ganglia of most monkeys at multiple intervals for the 12-month study period. SVV-specific antigens were detected in ganglia and liver during acute varicella, but not in ganglia 12 months p.i. Analysis of control tissue (ganglia, lung, and liver) from uninfected SVV-seronegative adult African green monkeys did not reveal SVV DNA, SVV RNA, SVV-specific antigen, or varicella-specific pathological changes. Overall, intratracheal inoculation of SVV in African green monkeys resulted in the presence of viral DNA and transcription of multiple viral genes in many tissues for months after experimental infection.

Persistence of simian varicella virus DNA in CD4(+) and CD8(+) blood mononuclear cells for years after intratracheal inoculation of African green monkeys.

Simian varicella virus (SVV) DNA was detected in blood mononuclear cells (MNCs) of adult African green monkeys 7 days to 23 months after intratracheal inoculation with 10(3) plaque forming units. Infectious virus was not detected in MNCs at 14 months postinfection (p.i.), and electron microscopic (EM) analysis of MNCs from two monkeys 21 months p.i. did not reveal virus particles. Real-time quantitative PCR analysis of DNA from blood MNCs taken at multiple intervals from SVV-infected monkeys M7 and M8 revealed a 10- to 100-fold decrease, but not clearance of SVV DNA in MNCs between 11 and 17 months p.i. Thereafter, the SVV DNA copy number did not decrease further between 17 and 23 months p.i. PCR analysis of MNCs sorted by flow cytometry revealed SVV DNA in T cells (CD4(+), CD8(+)) and B cells (CD20(+)), but not in monocyte-macrophages (CD14(+)), 10 days p.i. At 11 and 23 months p.i., SVV DNA was found exclusively in CD4(+) and CD8(+) T cells. Whether the detection of SVV DNA in CD4(+) and CD8(+) MNCs many months after the resolution of acute varicella reflects continued infection of these cells that began at the time of acute varicella or represents infection acquired by MNCs trafficking through infected tissues is unknown.