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 language | English (US) |
|---|---|
| Pages (from-to) | 589-598 |
| Number of pages | 10 |
| Journal | AIDS |
| Volume | 21 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 1 2007 |
| Externally published | Yes |
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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
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 journal › Article
}
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 -