Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract

Anuradha Rebbapragada, Charles Wachihi, Christopher Pettengell, Sherzana Sunderji, Sanja Huibner, Walter Jaoko, Blake Ball, Keith Fowke, Tony Mazzulli, Francis A. Plummer, Rupert Kaul

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

OBJECTIVE: There is substantial epidemiological evidence that infection by Herpes simplex virus type 2 (HSV2) enhances both HIV susceptibility and subsequent sexual transmission. Both infections are extremely common in female sex workers (FSWs) in sub-Saharan Africa, and up to 80% of new HIV infections in urban men in the region are acquired via transactional sex. The present study aimed to elucidate the mucosal immune interactions between HIV and HSV2 in the genital tract. METHODS: Endocervical immune cell populations, cytokine/chemokine protein levels in cervico-vaginal secretions and cervical immune gene expression profiles were measured in a well-defined cohort of HIV-infected and uninfected Kenyan FSWs. Associations between the genital immune milieu and infection by and/or shedding of common genital co-pathogens were examined. RESULTS: HIV-infected FSWs were much more likely to be infected by HSV2, and to shed HSV2 DNA in the genital tract. There was also a profound negative 'mucosal synergy' between these viruses. In HIV uninfected FSWs, HSV2 infection was associated with a ten-fold increase in cervical immature dendritic cells (iDC) expressing DC-SIGN, and a three-fold increase in cervical CD4+ T cells expressing CCR5. HIV infection was associated with iDC depletion in the cervix, and with increased HSV2 genital reactivation, which in turn was associated with HIV shedding levels. CONCLUSIONS: The findings suggest a mucosal vicious circle in which HSV2 infection increases HIV target cells in the genital mucosa, subsequent HIV infection impairs HSV2 mucosal immune control, and local HSV2 reactivation enhances both HSV2 and HIV transmission.

Original languageEnglish (US)
Pages (from-to)589-598
Number of pages10
JournalAIDS
Volume21
Issue number5
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Fingerprint

Herpes Simplex
HIV-2
Human Herpesvirus 2
HIV
Sex Workers
HIV Infections
Virus Diseases
Dendritic Cells
Infection
Africa South of the Sahara
Transcriptome
Chemokines
Cervix Uteri
Mucous Membrane
Cytokines
Viruses
T-Lymphocytes

Keywords

  • AIDS/HIV
  • Dendritic cells
  • Genital mucosa
  • Herpes simplex virus 2
  • Mucosal immunity
  • Susceptibility
  • Transmission

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Rebbapragada, A., Wachihi, C., Pettengell, C., Sunderji, S., Huibner, S., Jaoko, W., ... Kaul, R. (2007). Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract. AIDS, 21(5), 589-598. https://doi.org/10.1097/QAD.0b013e328012b896

Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract. / Rebbapragada, Anuradha; Wachihi, Charles; Pettengell, Christopher; Sunderji, Sherzana; Huibner, Sanja; Jaoko, Walter; Ball, Blake; Fowke, Keith; Mazzulli, Tony; Plummer, Francis A.; Kaul, Rupert.

In: AIDS, Vol. 21, No. 5, 01.03.2007, p. 589-598.

Research output: Contribution to journalArticle

Rebbapragada, A, Wachihi, C, Pettengell, C, Sunderji, S, Huibner, S, Jaoko, W, Ball, B, Fowke, K, Mazzulli, T, Plummer, FA & Kaul, R 2007, 'Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract', AIDS, vol. 21, no. 5, pp. 589-598. https://doi.org/10.1097/QAD.0b013e328012b896
Rebbapragada, Anuradha ; Wachihi, Charles ; Pettengell, Christopher ; Sunderji, Sherzana ; Huibner, Sanja ; Jaoko, Walter ; Ball, Blake ; Fowke, Keith ; Mazzulli, Tony ; Plummer, Francis A. ; Kaul, Rupert. / Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract. In: AIDS. 2007 ; Vol. 21, No. 5. pp. 589-598.
@article{e571cd00507740adadd762749b55bd86,
title = "Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract",
abstract = "OBJECTIVE: There is substantial epidemiological evidence that infection by Herpes simplex virus type 2 (HSV2) enhances both HIV susceptibility and subsequent sexual transmission. Both infections are extremely common in female sex workers (FSWs) in sub-Saharan Africa, and up to 80{\%} of new HIV infections in urban men in the region are acquired via transactional sex. The present study aimed to elucidate the mucosal immune interactions between HIV and HSV2 in the genital tract. METHODS: Endocervical immune cell populations, cytokine/chemokine protein levels in cervico-vaginal secretions and cervical immune gene expression profiles were measured in a well-defined cohort of HIV-infected and uninfected Kenyan FSWs. Associations between the genital immune milieu and infection by and/or shedding of common genital co-pathogens were examined. RESULTS: HIV-infected FSWs were much more likely to be infected by HSV2, and to shed HSV2 DNA in the genital tract. There was also a profound negative 'mucosal synergy' between these viruses. In HIV uninfected FSWs, HSV2 infection was associated with a ten-fold increase in cervical immature dendritic cells (iDC) expressing DC-SIGN, and a three-fold increase in cervical CD4+ T cells expressing CCR5. HIV infection was associated with iDC depletion in the cervix, and with increased HSV2 genital reactivation, which in turn was associated with HIV shedding levels. CONCLUSIONS: The findings suggest a mucosal vicious circle in which HSV2 infection increases HIV target cells in the genital mucosa, subsequent HIV infection impairs HSV2 mucosal immune control, and local HSV2 reactivation enhances both HSV2 and HIV transmission.",
keywords = "AIDS/HIV, Dendritic cells, Genital mucosa, Herpes simplex virus 2, Mucosal immunity, Susceptibility, Transmission",
author = "Anuradha Rebbapragada and Charles Wachihi and Christopher Pettengell and Sherzana Sunderji and Sanja Huibner and Walter Jaoko and Blake Ball and Keith Fowke and Tony Mazzulli and Plummer, {Francis A.} and Rupert Kaul",
year = "2007",
month = "3",
day = "1",
doi = "10.1097/QAD.0b013e328012b896",
language = "English (US)",
volume = "21",
pages = "589--598",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract

AU - Rebbapragada, Anuradha

AU - Wachihi, Charles

AU - Pettengell, Christopher

AU - Sunderji, Sherzana

AU - Huibner, Sanja

AU - Jaoko, Walter

AU - Ball, Blake

AU - Fowke, Keith

AU - Mazzulli, Tony

AU - Plummer, Francis A.

AU - Kaul, Rupert

PY - 2007/3/1

Y1 - 2007/3/1

N2 - OBJECTIVE: There is substantial epidemiological evidence that infection by Herpes simplex virus type 2 (HSV2) enhances both HIV susceptibility and subsequent sexual transmission. Both infections are extremely common in female sex workers (FSWs) in sub-Saharan Africa, and up to 80% of new HIV infections in urban men in the region are acquired via transactional sex. The present study aimed to elucidate the mucosal immune interactions between HIV and HSV2 in the genital tract. METHODS: Endocervical immune cell populations, cytokine/chemokine protein levels in cervico-vaginal secretions and cervical immune gene expression profiles were measured in a well-defined cohort of HIV-infected and uninfected Kenyan FSWs. Associations between the genital immune milieu and infection by and/or shedding of common genital co-pathogens were examined. RESULTS: HIV-infected FSWs were much more likely to be infected by HSV2, and to shed HSV2 DNA in the genital tract. There was also a profound negative 'mucosal synergy' between these viruses. In HIV uninfected FSWs, HSV2 infection was associated with a ten-fold increase in cervical immature dendritic cells (iDC) expressing DC-SIGN, and a three-fold increase in cervical CD4+ T cells expressing CCR5. HIV infection was associated with iDC depletion in the cervix, and with increased HSV2 genital reactivation, which in turn was associated with HIV shedding levels. CONCLUSIONS: The findings suggest a mucosal vicious circle in which HSV2 infection increases HIV target cells in the genital mucosa, subsequent HIV infection impairs HSV2 mucosal immune control, and local HSV2 reactivation enhances both HSV2 and HIV transmission.

AB - OBJECTIVE: There is substantial epidemiological evidence that infection by Herpes simplex virus type 2 (HSV2) enhances both HIV susceptibility and subsequent sexual transmission. Both infections are extremely common in female sex workers (FSWs) in sub-Saharan Africa, and up to 80% of new HIV infections in urban men in the region are acquired via transactional sex. The present study aimed to elucidate the mucosal immune interactions between HIV and HSV2 in the genital tract. METHODS: Endocervical immune cell populations, cytokine/chemokine protein levels in cervico-vaginal secretions and cervical immune gene expression profiles were measured in a well-defined cohort of HIV-infected and uninfected Kenyan FSWs. Associations between the genital immune milieu and infection by and/or shedding of common genital co-pathogens were examined. RESULTS: HIV-infected FSWs were much more likely to be infected by HSV2, and to shed HSV2 DNA in the genital tract. There was also a profound negative 'mucosal synergy' between these viruses. In HIV uninfected FSWs, HSV2 infection was associated with a ten-fold increase in cervical immature dendritic cells (iDC) expressing DC-SIGN, and a three-fold increase in cervical CD4+ T cells expressing CCR5. HIV infection was associated with iDC depletion in the cervix, and with increased HSV2 genital reactivation, which in turn was associated with HIV shedding levels. CONCLUSIONS: The findings suggest a mucosal vicious circle in which HSV2 infection increases HIV target cells in the genital mucosa, subsequent HIV infection impairs HSV2 mucosal immune control, and local HSV2 reactivation enhances both HSV2 and HIV transmission.

KW - AIDS/HIV

KW - Dendritic cells

KW - Genital mucosa

KW - Herpes simplex virus 2

KW - Mucosal immunity

KW - Susceptibility

KW - Transmission

UR - http://www.scopus.com/inward/record.url?scp=33847219957&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847219957&partnerID=8YFLogxK

U2 - 10.1097/QAD.0b013e328012b896

DO - 10.1097/QAD.0b013e328012b896

M3 - Article

C2 - 17314521

AN - SCOPUS:33847219957

VL - 21

SP - 589

EP - 598

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 5

ER -