title: Rectal HSV-2 Infection May Increase Rectal SIV Acquisition Even in the Context of SIVΔnef Vaccination.
abstract: Prevalent HSV-2 infection increases the risk of HIV acquisition both in men and women even in asymptomatic subjects. Understanding the impact of HSV-2 on the mucosal microenvironment may help to identify determinants of susceptibility to HIV. Vaginal HSV-2 infection increases the frequency of cells highly susceptible to HIV in the vaginal tissue of women and macaques and this correlates with increased susceptibility to vaginal SHIV infection in macaques. However, the effect of rectal HSV-2 infection on HIV acquisition remains understudied. We developed a model of rectal HSV-2 infection in macaques in combination with rectal SIVmac239Δnef (SIVΔnef) vaccination and our results suggest that rectal HSV-2 infection may increase the susceptibility of macaques to rectal SIVmac239 wild-type (wt) infection even in SIVΔnef-infected animals. Rectal SIVΔnef infection/vaccination protected 7 out of 7 SIVΔnef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIVΔnef-negative macaques), while 1 out of 3 animals co-infected with SIVΔnef and HSV-2 acquired SIVmac239wt infection. HSV-2/SIVmac239wt co-infected animals had increased concentrations of inflammatory factors in their plasma and rectal fluids and a tendency toward higher acute SIVmac239wt plasma viral load. However, they had higher blood CD4 counts and reduced depletion of CCR5+ CD4+ T cells compared to SIVmac239wt-only infected animals. Thus, rectal HSV-2 infection generates a pro-inflammatory environment that may increase susceptibility to rectal SIV infection and may impact immunological and virological parameters during acute SIV infection. Studies with larger number of animals are needed to confirm these findings.
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Natalia
authors.initials: N
authors.lastname: Guerra-Pérez
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Meropi
authors.initials: M
authors.lastname: Aravantinou
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Filippo
authors.initials: F
authors.lastname: Veglia
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Diana
authors.initials: D
authors.lastname: Goode
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Rosaline
authors.initials: R
authors.lastname: Truong
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Nina
authors.initials: N
authors.lastname: Derby
authors.affiliation: Tulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.affiliation: Tulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.
authors.forename: Brooke
authors.initials: B
authors.lastname: Grasperge
authors.affiliation: Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York, United States of America.
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Robbiani
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Elena
authors.initials: E
authors.lastname: Martinelli
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D060085:Coinfection / Q000097:blood / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D015693:Gene Products, nef / Q000378:metabolism*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D010641:Phenotype; D012007:Rectum / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014611:Vaccination; D019562:Viral Load / Q000276:immunology
chemical_list: D016207:Cytokines; D015693:Gene Products, nef