Virus-specific immune memory at peripheral sites of Herpes Simplex Virus type 2 (HSV-2) infection in Guinea pigs

Jingya Xia, Ronald L. Veselenak, Summer R. Gorder, Nigel Bourne, Gregg Milligan

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere114652
JournalPLoS One
Volume9
Issue number12
DOIs
StatePublished - Dec 8 2014

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Human herpesvirus 2
Computer peripheral equipment
Human Herpesvirus 2
Virus Diseases
Viruses
guinea pigs
Guinea Pigs
Data storage equipment
viruses
infection
Tissue
spinal cord
genitalia
Spinal Cord
T-cells
Virus Latency
Sensory Ganglia
Antibody-Producing Cells
spleen
antibodies

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Virus-specific immune memory at peripheral sites of Herpes Simplex Virus type 2 (HSV-2) infection in Guinea pigs. / Xia, Jingya; Veselenak, Ronald L.; Gorder, Summer R.; Bourne, Nigel; Milligan, Gregg.

In: PLoS One, Vol. 9, No. 12, e114652, 08.12.2014.

Research output: Contribution to journalArticle

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