title: 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.
abstract: 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 < or = 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.
authors: Laboratoire de Virologie Médicale, Hôpital Robert Debré, Centre Hospitalo-Universitaire de Reims, et Equipe d'Accueil 3798, Faculté de Médecine de Reims, France. landreoletti@chu-reims.fr
authors: Laurent
authors: L
authors: Andreoletti
authors: Katharina
authors: K
authors: Skrabal
authors: Virginie
authors: V
authors: Perrin
authors: Nicolas
authors: N
authors: Chomont
authors: Sentob
authors: S
authors: Saragosti
authors: Gerard
authors: G
authors: Gresenguet
authors: Helene
authors: H
authors: Moret
authors: Jerome
authors: J
authors: Jacques
authors: Jean de Dieu
authors: Jde D
authors: Longo
authors: Mathieu
authors: M
authors: Matta
authors: Fabrizio
authors: F
authors: Mammano
authors: Laurent
authors: L
authors: Belec
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D002584:Cervix Uteri / Q000821:virology*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000503:physiopathology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood*; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014621:Vagina / Q000821:virology*
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4