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Mathematical Modeling Predicts that Increased HSV-2 Shedding in HIV-1 Infected Persons Is Due to Poor Immunologic Control in Ganglia and Genital Mucosa

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  • Joshua T Schiffer
  • David A Swan
  • Amalia Magaret
  • Timothy W Schacker
  • Anna Wald
  • Lawrence Corey

Abstract

A signature feature of HIV infection is poor control of herpes virus infections, which reactivate from latency and cause opportunistic infections. While the general mechanism underlying this observation is deficient CD4+T-cell function, it is unknown whether increased severity of herpes virus infections is due primarily to poor immune control in latent or lytic sites of infection, or whether CD4+ immunodeficiency leads to more critical downstream deficits in humoral or cell-mediated immunologic responses. Here we compare genital shedding patterns of herpes simplex virus-2 (HSV-2) in 98 HIV infected and 98 HIV uninfected men matched on length of infection, HSV-1 serostatus and nationality. We demonstrate that high copy HSV-2 shedding is more frequent in HIV positive men, particularly in participants with CD4+ T-cell count

Suggested Citation

  • Joshua T Schiffer & David A Swan & Amalia Magaret & Timothy W Schacker & Anna Wald & Lawrence Corey, 2016. "Mathematical Modeling Predicts that Increased HSV-2 Shedding in HIV-1 Infected Persons Is Due to Poor Immunologic Control in Ganglia and Genital Mucosa," PLOS ONE, Public Library of Science, vol. 11(6), pages 1-22, June.
    • Handle: RePEc:plo:pone00:0155124
    DOI: 10.1371/journal.pone.0155124
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    References listed on IDEAS

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    1. Varsha Dhankani & J Nathan Kutz & Joshua T Schiffer, 2014. "Herpes Simplex Virus-2 Genital Tract Shedding Is Not Predictable over Months or Years in Infected Persons," PLOS Computational Biology, Public Library of Science, vol. 10(11), pages 1-16, November.
    2. Haina Shin & Akiko Iwasaki, 2012. "A vaccine strategy that protects against genital herpes by establishing local memory T cells," Nature, Nature, vol. 491(7424), pages 463-467, November.
    3. Jia Zhu & Tao Peng & Christine Johnston & Khamsone Phasouk & Angela S. Kask & Alexis Klock & Lei Jin & Kurt Diem & David M. Koelle & Anna Wald & Harlan Robins & Lawrence Corey, 2013. "Immune surveillance by CD8αα+ skin-resident T cells in human herpes virus infection," Nature, Nature, vol. 497(7450), pages 494-497, May.
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