Simian Varicella Virus Is Present in Macrophages, Dendritic Cells, and T Cells in Lymph Nodes of Rhesus Macaques after Experimental Reactivation

Author:

Traina-Dorge Vicki1,Doyle-Meyers Lara A.2,Sanford Robert3,Manfredo Jennifer4,Blackmon Anna4,Wellish Mary4,James Stephanie4,Alvarez Xavier5,Midkiff Cecily5,Palmer Brent E.6,Deharo Eileen1,Gilden Don47,Mahalingam Ravi4

Affiliation:

1. Division of Microbiology, Tulane University, Tulane National Primate Research Center, Covington, Louisiana, USA

2. Division of Veterinary Medicine, Tulane University, Tulane National Primate Research Center, Covington, Louisiana, USA

3. Tulane Cancer Center, Tulane School of Medicine, New Orleans, Louisiana, USA

4. Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA

5. Division of Comparative Pathology, Tulane University, Tulane National Primate Research Center, Covington, Louisiana, USA

6. Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA

7. Department of Immunology & Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA

Abstract

ABSTRACT 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 revealed SVV antigen in the lung alveolar wall, in ganglionic neurons and nonneuronal cells, and in skin and in lymph nodes. In skin, SVV was found primarily in sweat glands. In lymph nodes, the SVV antigen colocalized mostly with macrophages, dendritic cells, and, to a lesser extent, T cells. The presence of SVV in lymph nodes, as verified by quantitative PCR detection of SVV DNA, might reflect the sequestration of virus by macrophages and dendritic cells in lymph nodes or the presentation of viral antigens to T cells to initiate an immune response against SVV, or both. IMPORTANCE VZV causes varicella (chickenpox), becomes latent in ganglia, and reactivates to produce zoster and multiple other serious neurological disorders. SVV in nonhuman primates has proved to be a useful model in which the pathogenesis of the virus parallels the pathogenesis of VZV in humans. Here, we show that SVV antigens are present in sweat glands in skin and in macrophages and dendritic cells in lymph nodes after SVV reactivation in monkeys, raising the possibility that macrophages and dendritic cells in lymph nodes serve as antigen-presenting cells to activate T cell responses against SVV after reactivation.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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