Interference with Major Histocompatibility Complex Class II-Restricted Antigen Presentation in the Brain by Herpes Simplex Virus Type 1: A Possible Mechanism of Evasion of the Immune Response

• Published in: Proceedings of the National Academy of Sciences - PNAS 1993-03, Vol.90 (5), p.2005-2009
• Main Authors: Lewandowski, Gail A., Lo, David, Bloom, Floyd E.
• Format: Article
• Language: English
• Subjects: Animals; Antigen presentation; Antigen-Presenting Cells - immunology; Biological and medical sciences; Brain; Brain - immunology; Brain - microbiology; CD4-Positive T-Lymphocytes - immunology; CD8 Antigens - analysis; Central nervous system; Female; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Herpes Simplex - immunology; herpes simplex virus 1; Herpes viruses; Histocompatibility antigens class II; Histocompatibility Antigens Class II - immunology; Human herpesvirus 1; Immune response; Infections; Medical research; Mice; Mice, Inbred BALB C; Mice, Nude; Microbiology; Nervous system; Neurology; Neurons; Opportunistic Infections - immunology; Opportunistic Infections - microbiology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Simplexvirus - immunology; T lymphocytes; T-Lymphocyte Subsets - immunology; Viral infections; Virology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.5.2005

Host survival of herpes simplex virus type 1 (HSV-1) infection depends on the establishment of latent infections in both peripheral and central nervous systems. Strains of HSV-1 that are successful in escaping the immune response produce a lethal infection. We now report a possible mechanism of immune response evasion used by HSV-1. After intraocular inoculation of mice, HSV-1 strain F established a latent infection in the brain, whereas strain KOS did not. The immune response to HSV-1 infection (strains KOS and F) in the brain was characterized by induction of major histocompatibility complex class II expression and recruitment of CD4+and CD8+cells to highly restricted sites of intracerebral viral infection. Major histocompatibility complex class II antigen expression was primarily intracellular in strain KOS infection centers and at the cell surface in strain F infection centers. We propose that major histocompatibility complex class II-restricted viral-antigen presentation to T cells is interrupted during strain KOS infections, thereby allowing KOS infection to evade T-cell-mediated events that would normally protect the host from a lethal infection. Immunocompromised mice (athymic or irradiated mice) could not survive strain F infections; however, latent F infections were established in irradiated mice reconstituted with naive lymph node and spleen cells. These data suggest that class II-restricted presentation of viral antigens is required for the control of HSV-1 infections in the nervous system.