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.
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.
Andreoletti
Laurent
L
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
Skrabal
Katharina
K
Perrin
Virginie
V
Chomont
Nicolas
N
Saragosti
Sentob
S
Gresenguet
Gerard
G
Moret
Helene
H
Jacques
Jerome
J
Longo
Jean de Dieu
Jde D
Matta
Mathieu
M
Mammano
Fabrizio
F
Belec
Laurent
L
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*
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4