Impact of Herpes Simplex Virus Type 2 and Human Immunodeficiency Virus Dual Infection on Female Genital Tract Mucosal Immunity and the Vaginal Microbiome

Marla J. Keller, Ashley Huber, Lilia Espinoza, Myrna G. Serrano, Hardik I. Parikh, Gregory A. Buck, Jeremy A. Gold, Yiqun Wu, Tao Wang, Betsy Herold

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Mechanisms linking herpes simplex virus type 2 (HSV-2) with human immunodeficiency virus (HIV) are not fully defined. We tested the hypothesis that HSV-2 and HIV dual infection is associated with cervicovaginal inflammation and/or vaginal dysbiosis. METHODS: Genital tract samples were obtained weekly over a 12-week period from 30 women seropositive (+) for HIV and HSV-2 and 15 women each who were seropositive for one or seronegative (-) for both viruses. Immune mediators, antimicrobial activity, and microbial composition and diversity were compared. RESULTS: Significant differences in the concentrations of interferon-γ (P = .002), tumor necrosis factor-α (P = .03), human beta defensin 1 (P = .001), secretory leukocyte protease inhibitor (P = .01), and lysozyme (P = .03) were observed across the 4 groups (Kruskal-Wallis). There were also significant differences in vaginal microbial alpha diversity (Simpson index) (P = .0046). Specifically, when comparing HIV-1+/HSV-2+ to HIV-1-/HSV-2- women, a decrease in Lactobacillus crispatus and increase in diverse anaerobes was observed. The number of genital HSV outbreaks was greater in HIV+ versus HIV- women (39 versus 12) (P = .04), but there were no significant differences when comparing outbreak to non-outbreak visits. CONCLUSIONS: Increased microbial diversity and cervicovaginal inflammation in HIV and HSV-2 dually infected women may adversely impact genital health and, in the absence of antiretroviral therapy, facilitate HIV shedding.

Original languageEnglish (US)
Pages (from-to)852-861
Number of pages10
JournalThe Journal of infectious diseases
Volume220
Issue number5
DOIs
StatePublished - Jul 31 2019

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Mucosal Immunity
Human Herpesvirus 2
Microbiota
Virus Diseases
HIV
Disease Outbreaks
HIV-1
Secretory Leukocyte Peptidase Inhibitor
Dysbiosis
Inflammation
Virus Shedding
Muramidase
Interferons
Tumor Necrosis Factor-alpha
Viruses
Health

Keywords

  • herpes simplex virus
  • human immunodeficiency virus
  • microbiome
  • mucosal immunity
  • vaginal dysbiosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Impact of Herpes Simplex Virus Type 2 and Human Immunodeficiency Virus Dual Infection on Female Genital Tract Mucosal Immunity and the Vaginal Microbiome. / Keller, Marla J.; Huber, Ashley; Espinoza, Lilia; Serrano, Myrna G.; Parikh, Hardik I.; Buck, Gregory A.; Gold, Jeremy A.; Wu, Yiqun; Wang, Tao; Herold, Betsy.

In: The Journal of infectious diseases, Vol. 220, No. 5, 31.07.2019, p. 852-861.

Research output: Contribution to journalArticle

Keller, Marla J. ; Huber, Ashley ; Espinoza, Lilia ; Serrano, Myrna G. ; Parikh, Hardik I. ; Buck, Gregory A. ; Gold, Jeremy A. ; Wu, Yiqun ; Wang, Tao ; Herold, Betsy. / Impact of Herpes Simplex Virus Type 2 and Human Immunodeficiency Virus Dual Infection on Female Genital Tract Mucosal Immunity and the Vaginal Microbiome. In: The Journal of infectious diseases. 2019 ; Vol. 220, No. 5. pp. 852-861.
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abstract = "BACKGROUND: Mechanisms linking herpes simplex virus type 2 (HSV-2) with human immunodeficiency virus (HIV) are not fully defined. We tested the hypothesis that HSV-2 and HIV dual infection is associated with cervicovaginal inflammation and/or vaginal dysbiosis. METHODS: Genital tract samples were obtained weekly over a 12-week period from 30 women seropositive (+) for HIV and HSV-2 and 15 women each who were seropositive for one or seronegative (-) for both viruses. Immune mediators, antimicrobial activity, and microbial composition and diversity were compared. RESULTS: Significant differences in the concentrations of interferon-γ (P = .002), tumor necrosis factor-α (P = .03), human beta defensin 1 (P = .001), secretory leukocyte protease inhibitor (P = .01), and lysozyme (P = .03) were observed across the 4 groups (Kruskal-Wallis). There were also significant differences in vaginal microbial alpha diversity (Simpson index) (P = .0046). Specifically, when comparing HIV-1+/HSV-2+ to HIV-1-/HSV-2- women, a decrease in Lactobacillus crispatus and increase in diverse anaerobes was observed. The number of genital HSV outbreaks was greater in HIV+ versus HIV- women (39 versus 12) (P = .04), but there were no significant differences when comparing outbreak to non-outbreak visits. CONCLUSIONS: Increased microbial diversity and cervicovaginal inflammation in HIV and HSV-2 dually infected women may adversely impact genital health and, in the absence of antiretroviral therapy, facilitate HIV shedding.",
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T1 - Impact of Herpes Simplex Virus Type 2 and Human Immunodeficiency Virus Dual Infection on Female Genital Tract Mucosal Immunity and the Vaginal Microbiome

AU - Keller, Marla J.

AU - Huber, Ashley

AU - Espinoza, Lilia

AU - Serrano, Myrna G.

AU - Parikh, Hardik I.

AU - Buck, Gregory A.

AU - Gold, Jeremy A.

AU - Wu, Yiqun

AU - Wang, Tao

AU - Herold, Betsy

PY - 2019/7/31

Y1 - 2019/7/31

N2 - BACKGROUND: Mechanisms linking herpes simplex virus type 2 (HSV-2) with human immunodeficiency virus (HIV) are not fully defined. We tested the hypothesis that HSV-2 and HIV dual infection is associated with cervicovaginal inflammation and/or vaginal dysbiosis. METHODS: Genital tract samples were obtained weekly over a 12-week period from 30 women seropositive (+) for HIV and HSV-2 and 15 women each who were seropositive for one or seronegative (-) for both viruses. Immune mediators, antimicrobial activity, and microbial composition and diversity were compared. RESULTS: Significant differences in the concentrations of interferon-γ (P = .002), tumor necrosis factor-α (P = .03), human beta defensin 1 (P = .001), secretory leukocyte protease inhibitor (P = .01), and lysozyme (P = .03) were observed across the 4 groups (Kruskal-Wallis). There were also significant differences in vaginal microbial alpha diversity (Simpson index) (P = .0046). Specifically, when comparing HIV-1+/HSV-2+ to HIV-1-/HSV-2- women, a decrease in Lactobacillus crispatus and increase in diverse anaerobes was observed. The number of genital HSV outbreaks was greater in HIV+ versus HIV- women (39 versus 12) (P = .04), but there were no significant differences when comparing outbreak to non-outbreak visits. CONCLUSIONS: Increased microbial diversity and cervicovaginal inflammation in HIV and HSV-2 dually infected women may adversely impact genital health and, in the absence of antiretroviral therapy, facilitate HIV shedding.

AB - BACKGROUND: Mechanisms linking herpes simplex virus type 2 (HSV-2) with human immunodeficiency virus (HIV) are not fully defined. We tested the hypothesis that HSV-2 and HIV dual infection is associated with cervicovaginal inflammation and/or vaginal dysbiosis. METHODS: Genital tract samples were obtained weekly over a 12-week period from 30 women seropositive (+) for HIV and HSV-2 and 15 women each who were seropositive for one or seronegative (-) for both viruses. Immune mediators, antimicrobial activity, and microbial composition and diversity were compared. RESULTS: Significant differences in the concentrations of interferon-γ (P = .002), tumor necrosis factor-α (P = .03), human beta defensin 1 (P = .001), secretory leukocyte protease inhibitor (P = .01), and lysozyme (P = .03) were observed across the 4 groups (Kruskal-Wallis). There were also significant differences in vaginal microbial alpha diversity (Simpson index) (P = .0046). Specifically, when comparing HIV-1+/HSV-2+ to HIV-1-/HSV-2- women, a decrease in Lactobacillus crispatus and increase in diverse anaerobes was observed. The number of genital HSV outbreaks was greater in HIV+ versus HIV- women (39 versus 12) (P = .04), but there were no significant differences when comparing outbreak to non-outbreak visits. CONCLUSIONS: Increased microbial diversity and cervicovaginal inflammation in HIV and HSV-2 dually infected women may adversely impact genital health and, in the absence of antiretroviral therapy, facilitate HIV shedding.

KW - herpes simplex virus

KW - human immunodeficiency virus

KW - microbiome

KW - mucosal immunity

KW - vaginal dysbiosis

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