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Clin Microbiol Infect. 2015 Sep;21(9):873.e1-9. doi: 10.1016/j.cmi.2015.05.014. Epub 2015 May 21.

Variability of human immunodeficiency virus-1 in the female genital reservoir during genital reactivation of herpes simplex virus type 2.

Author information

1
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.
2
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.
3
Département des Sciences Biologiques et Centre de recherche BioMed, Université du Québec à Montréal (UQAM), Montreal, Quebec, Canada.
4
Université Paris Diderot, Sorbonne Paris Cité, Inserm IAME, UMR 1137, F-75018 Paris, France; AP-HP, Hôpital Bichat, Laboratoire de Virologie, Paris, France.
5
Université Lyon 1 - Claude Bernard, Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, F-69622 Villeurbanne, France.
6
Université de Picardie Jules Verne, EA 4666 'Lymphocyte Normal/Pathologique et Cancers', UFR de Médecine, Amiens, France.
7
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.
8
Département de Microbiologie et d'Infectiologie, Faculté de Médecine, Centre for International Health, University of Sherbrooke, Sherbrooke, Quebec, Canada.
9
Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
10
Laboratoire de Virologie, Hôpital Européen Georges Pompidou, and Université Paris Descartes (Paris V), Paris Sorbonne Cité, Paris, France.

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.

KEYWORDS:

Africa; HIV-1; HSV-2; Herpes simplex virus; genital herpes; phylogeny; variability

PMID:
26003280
DOI:
10.1016/j.cmi.2015.05.014
[Indexed for MEDLINE]
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