title: Variability of human immunodeficiency virus-1 in the female genital reservoir during genital reactivation of herpes simplex virus type 2.
abstract: Clinical and subclinical genital herpes simplex virus type 2 (HSV-2) reactivations have been associated with increases in human immunodeficiency virus (HIV)-1 genital shedding. Whether HSV-2 shedding contributes to the selection of specific genital HIV-1 variants remains unknown. We evaluated the genetic diversity of genital and blood HIV-1 RNA and DNA in 14 HIV-1/HSV-2-co-infected women, including seven with HSV-2 genital reactivation, and seven without as controls. HIV-1 DNA and HIV-1 RNA env V1-V3 sequences in paired blood and genital samples were compared. The HSV-2 selection pressure on HIV was estimated according to the number of synonymous substitutions (dS), the number of non-synonymous substitutions (dN) and the dS/dN ratio within HIV quasi-species. HIV-1 RNA levels in cervicovaginal secretions were higher in women with HSV-2 replication than in controls (p0.02). Plasma HIV-1 RNA and genital HIV-1 RNA and DNA were genetically compartmentalized. No differences in dS, dN and the dS/dN ratio were observed between the study groups for either genital HIV-1 RNA or plasma HIV-1 RNA. In contrast, dS and dN in genital HIV-1 DNA were significantly higher in patients with HSV-2 genital reactivation (p <0.01 and p <0.05, respectively). The mean of the dS/dN ratio in genital HIV-1 DNA was slightly higher in patients with HSV-2 genital replication, indicating a trend for purifying selection (p 0.056). HSV-2 increased the genetic diversity of genital HIV-1 DNA. These observations confirm molecular interactions between HSV-2 and HIV-1 at the genital tract level.
authors.affiliation: Université Paris Diderot, Sorbone Paris Cité, Inserm U941, APHP, Laboratoire de Virologie, Hôpital Saint-Louis, Paris, France. Electronic address: jerome.le-goff@sls.aphp.fr.
authors.forename: J
authors.initials: J
authors.lastname: LeGoff
authors.affiliation: Commissariat à l'Energie Atomique, Division of Immuno-Virologie, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses, France; Université Paris SudXI, Inserm IMVA, UMR 1184 Orsay, France.
authors.forename: P
authors.initials: P
authors.lastname: Roques
authors.affiliation: Département des Sciences Biologiques et Centre de recherche BioMed, Université du Québec à Montréal (UQAM), Montreal, Quebec, Canada.
authors.forename: M-A
authors.initials: MA
authors.lastname: Jenabian
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Inserm IAME, UMR 1137, F-75018 Paris, France; AP-HP, Hôpital Bichat, Laboratoire de Virologie, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Charpentier
authors.affiliation: Université Lyon 1 - Claude Bernard, Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, F-69622 Villeurbanne, France.
authors.forename: C
authors.initials: C
authors.lastname: Brochier
authors.affiliation: Université de Picardie Jules Verne, EA 4666 'Lymphocyte Normal/Pathologique et Cancers', UFR de Médecine, Amiens, France.
authors.forename: H
authors.initials: H
authors.lastname: Bouhlal
authors.affiliation: Centre National de Référence des Maladies Sexuellement Transmissibles et du SIDA de Bangui and Unité de Recherches et d'Intervention sur les Maladies Sexuellement Transmissibles et du SIDA, Faculté des Sciences de la Santé, Bangui, Central African Republic.
authors.forename: G
authors.initials: G
authors.lastname: Gresenguet
authors.affiliation: Département de Microbiologie et d'Infectiologie, Faculté de Médecine, Centre for International Health, University of Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Frost
authors.affiliation: Département de Microbiologie et d'Infectiologie, Faculté de Médecine, Centre for International Health, University of Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Pepin
authors.affiliation: Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Mayaud
authors.affiliation: Laboratoire de Virologie, Hôpital Européen Georges Pompidou, and Université Paris Descartes (Paris V), Paris Sorbonne Cité, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Belec
mesh_terms: D001769:Blood / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D005122:Exudates and Transudates / Q000821:virology; D005260:Female; D014644:Genetic Variation; D005836:Genitalia, Female / Q000821:virology*; D015658:HIV Infections / Q000150:complications* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006558:Herpes Genitalis / Q000150:complications*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D059645:Mutation Rate; D012367:RNA, Viral / Q000235:genetics; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D019562:Viral Load; D014775:Virus Activation; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: Africa; HIV-1; HSV-2; Herpes simplex virus; genital herpes; phylogeny; variability