title: MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa.
abstract: The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV), and human papillomavirus. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection, and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and human papillomavirus in murine models. Recently, we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants. Here we established models of ex vivo SHIV-RT/HSV-2 coinfection of vaginal mucosa and SHIV-RT infection of rectal mucosa in macaques (challenge of rectal mucosa with HSV-2 did not result in reproducible tissue infection), evaluated antiviral activity of MZC, and compared quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay readouts for monitoring SHIV-RT infection. MZC (at nontoxic dilutions) significantly inhibited SHIV-RT in vaginal and rectal mucosas and HSV-2 in vaginal mucosa when present during viral challenge. Analysis of SHIV-RT infection and MZC activity by 1-step simian immunodeficiency virus gag quantitative RT-PCR and p27 enzyme-linked immunosorbent assay demonstrated similar virus growth dynamics and MZC activity by both methods and higher sensitivity of quantitative RT-PCR. Our data provide more evidence that MZC is a promising dual compartment multipurpose prevention technology candidate.
authors.affiliation: *Population Council, New York, NY; †BioRad Laboratories, Hercules, CA; ‡Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY; and §Tulane National Primate Research Center, Tulane University, Covington, LA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Calenda
authors.forename: Guillermo
authors.initials: G
authors.lastname: Villegas
authors.forename: Patrick
authors.initials: P
authors.lastname: Barnable
authors.forename: Claudia
authors.initials: C
authors.lastname: Litterst
authors.forename: Keith
authors.initials: K
authors.lastname: Levendosky
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cooney
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.forename: José A
authors.initials: JA
authors.lastname: Fernández-Romero
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Zydowsky
authors.forename: Natalia
authors.initials: N
authors.lastname: Teleshova
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D005260:Female; D005782:Gels / Q000494:pharmacology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000254:growth & development; D008251:Macaca; D008826:Microbial Sensitivity Tests; D008962:Models, Theoretical; D009092:Mucous Membrane / Q000821:virology*; D009924:Organ Culture Techniques; D011725:Pyridines / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000032:analysis*; D012007:Rectum / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000201:enzymology* / Q000254:growth & development; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014621:Vagina / Q000821:virology
chemical_list: D000998:Antiviral Agents; D005782:Gels; C510296:MIV 150; D011725:Pyridines; D014508:Urea; D012194:RNA-Directed DNA Polymerase