Genital Herpes simplex virus Type 2 infection in humanized HIV-transgenic mice triggers HIV shedding and is associated with greater neurological disease

Briana Nixon, Esra Fakioglu, Martha Stefanidou, Yanhua Wang, Monica Dutta, Harris Goldstein, Betsy C. Herold

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background. Epidemiological studies consistently demonstrate synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1). Higher HIV-1 loads are observed in coinfected individuals, and conversely, HIV-1 is associated with more-severe herpetic disease. A small animal model of coinfection would facilitate identification of the biological mechanisms underlying this synergy and provide the opportunity to evaluate interventions.Methods. Mice transgenic for HIV-1 provirus and human cyclin T1 under the control of a CD4 promoter (JR-CSF/hu-cycT1) were intravaginally infected with HSV-2 and evaluated for disease progression, HIV shedding, and mucosal immune responses.Results. HSV-2 infection resulted in higher vaginal HIV loads and genital tissue expression of HIV RNA, compared with HSV-uninfected JR-CSF/hu-cycT1 mice. There was an increase in genital tract inflammatory cells, cytokines, chemokines, and interferons in response to HSV-2, although the kinetics of the response were delayed in HIV-transgenic, compared with control mice. Moreover, the JR-CSF/hu-cycT1 mice exhibited earlier and more-severe neurological disease. The latter was associated with downregulation of secretory leukocyte protease inhibitor expression in neuronal tissue, a molecule with antiinflammatory, antiviral, and neuroprotective properties.Conclusions. JR-CSF/hu-cycT1 mice provide a valuable model to study HIV/HSV-2 coinfection and identify potential mechanisms by which HSV-2 facilitates HIV-1 transmission and HIV modulates HSV-2-mediated disease.

Original languageEnglish (US)
Pages (from-to)510-522
Number of pages13
JournalJournal of Infectious Diseases
Volume209
Issue number4
DOIs
Publication statusPublished - Feb 15 2014

    Fingerprint

Keywords

  • coinfection
  • female genital tract
  • herpes simplex virus-2
  • human immunodeficiency virus-1
  • mouse model
  • sexually transmitted infections

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this