title: Virus-specific immune memory at peripheral sites of herpes simplex virus type 2 (HSV-2) infection in guinea pigs.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Jingya
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Veselenak
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Summer R
authors.initials: SR
authors.lastname: Gorder
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States of America; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Nigel
authors.initials: N
authors.lastname: Bourne
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States of America; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Gregg N
authors.initials: GN
authors.lastname: Milligan
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005260:Female; D005434:Flow Cytometry; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000276:immunology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D009928:Organ Specificity; D014709:Vero Cells; D017201:Virus Shedding / Q000276:immunology*