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Vaginal Product Formulation Alters the Innate Antiviral Activity and Glycome of Cervicovaginal Fluids with Implications for Viral Susceptibility.

Abstract：

:Glycosylated proteins (i.e., mucins, IgG) are important mediators of innate antiviral immunity in the vagina; however, our current knowledge of the role that glycan themselves play in genital immunity is relatively low. Herein, we evaluate the relationship between innate antiviral immunity and glycomic composition in cervicovaginal lavage fluid (CVL) collected as part of a Phase I clinical trial testing the impact of two distinct formulations of the antiretroviral drug dapivirine. Using lectin microarray technology, we discovered that formulation (hydrogel- versus film-based delivery) impacted the CVL glycome, with hydrogel formulations inducing more changes, including a loss of high-mannose. The loss of this epitope correlated to a loss of anti-HIV-1 activity. Glycoproteomic identification of high-mannose proteins revealed a cohort of antiproteases shown to be important in HIV-1 resistance, whose expression covaried with the high-mannose signature. Our data strongly suggests high-mannose as a marker for secreted proteins mediating innate antiviral immunity in vaginal fluids and that drug formulation may impact this activity as reflected in the glycome.

journal_name

ACS Infect Dis

journal_title

ACS infectious diseases

authors

Koppolu S,Wang L,Mathur A,Nigam JA,Dezzutti CS,Isaacs C,Meyn L,Bunge KE,Moncla BJ,Hillier SL,Rohan LC,Mahal LK

doi

10.1021/acsinfecdis.8b00157

subject

Has Abstract

pub_date

2018-11-09 00:00:00

pages

1613-1622

issue

11

issn

2373-8227

journal_volume

4

pub_type

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