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Journal of Clinical Microbiology, June 2007, p. 1838-1842, Vol. 45, No. 6
0095-1137/07/$08.00+0     doi:10.1128/JCM.00113-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Genetic and Phenotypic Features of Blood and Genital Viral Populations of Clinically Asymptomatic and Antiretroviral-Treatment-Naive Clade A Human Immunodeficiency Virus Type 1-Infected Women

Laboratoire de Virologie Médicale, Hôpital Robert Debré, Centre Hospitalo-Universitaire de Reims, et Equipe d'Accueil 3798, Faculté de Médecine de Reims, France,¹ INSERM U552-Recherche Antivirale, Hôpital Bichat-Claude Bernard, Paris, France,² Unité Immunité et Biothérapie Muqueuse, Centre de Recherches Biomédicales des Cordeliers, Université René Descartes (Paris V), Paris, France,³ Unité de Recherche et d'Intervention sur les Maladies Sexuellement Transmissibles et le SIDA, Faculté des Sciences de la Santé, and Centre National de Référence des Maladies Sexuellement Transmissibles et du SIDA, Bangui, République Centrafricaine⁴

Received 16 January 2007/ Returned for modification 4 March 2007/ Accepted 16 April 2007

In the present study, we assessed whether human immunodeficiency virus type 1 (HIV-1) genetic compartmentalization was associated with phenotypic CCR5 (R5) or CXCR4 (X4) coreceptor usage differences between the systemic and the genital viral populations. Four clinically asymptomatic and treatment-naïve clade A HIV-1-infected patients were selected from a cohort of 274 African women, because they were free of all the biological cofactors known to modify the kinetics of viral production in the genital tract. HIV RNA envelope sequences (V1 to V3) derived from plasma and cervicovaginal secretions (CVS) were amplified, subcloned, and sequenced. CCR5 or CXCR4 coreceptor usage was determined by production of recombinant viral particles, followed by single-cycle infection assays of indicator cell lines, using the tropism recombinant test. In these four selected patients, CVS-derived sequences appeared to be genetically distinct from blood-derived sequences (P 0.001). Two patients were found to harbor virus populations with only the R5 phenotype in both compartments, whereas viruses using CXCR4 in addition to CCR5 were detected in two other patients. In particular, one woman harbored genital virus populations with mixed R5 and X4 phenotypes associated with peripheral blood populations with only the R5 phenotype. These results demonstrate genetic compartmentalization of HIV between the plasma and genital secretions of clinically asymptomatic, treatment-naïve, clade A-infected women. Also, for one patient, we report phenotypic coreceptor usage differences between the systemic (R5) and genital (R5/X4) viral populations. These features may be critical for the development of further mucosal vaccines, therapies, or new preventive strategies to block heterosexual transmission.

Published ahead of print on 25 April 2007.

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