Virus-specific immune memory at peripheral sites of herpes simplex virus type 2 (HSV-2) infection in guinea pigs

• Published in: PloS one Vol. 9; no. 12; p. e114652
• Main Authors: Xia, Jingya, Veselenak, Ronald L, Gorder, Summer R, Bourne, Nigel, Milligan, Gregg N
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08-12-2014; Public Library of Science (PLoS)
• Subjects: Activation; Adaptive immunity; Animal tissues; Animals; Antibodies; Antibody-Producing Cells - immunology; B cells; Biology and Life Sciences; Bone marrow; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; Cells, Cultured; Cercopithecus aethiops; Cervix; Computer memory; Female; Flow Cytometry; Ganglia; Genital tract; Glycoproteins; Guinea Pigs; Herpes Genitalis - immunology; Herpes Genitalis - virology; Herpes simplex; Herpesvirus 2, Human - immunology; Immune response; Immune system; Immunologic Memory - immunology; Immunological memory; Infection; Infections; Latency; Lymphocytes; Lymphocytes B; Lymphocytes T; Medicine and health sciences; Memory cells; Organ Specificity; Pathogenesis; Plasma cells; Populations; Research and Analysis Methods; Sensory neurons; Spinal cord; Spleen; T cells; Uterus; Vagina; Vero Cells; Virus Shedding - immunology; Viruses; γ-Interferon; United States > US; Texas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0114652

Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4+ and CD8+ resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the setting of HSV-2 latency and spontaneous reactivation.