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

被引:19
作者
Andreoletti, Laurent
Skrabal, Katharma
Perrin, Virginie
Chomont, Nicolas
Saragosti, Sentob
Gresenguet, Gerard
Moret, Helene
Jacques, Jerome
Longo, Jean de Dieu
Matta, Mathieu
Mammano, Fabrizio
Belec, Laurent
机构
[1] Hop Robert Debre, CHU Reims, Med Virol Lab, Reims, France
[2] Fac Med, Equipe Accueil 3798, Reims, France
[3] Hop Bichat Claude Bernard, INSERM, Rech Antivirale U552, F-75877 Paris 18, France
[4] Univ Paris 05, Ctr Rech Biomed Cordeliers, Unite Immunite & Biotherapie Muqueuse, Paris, France
[5] Fac Sci Sante, Unite Rech & Intervent Malad Sexuellement Transmi, Bangui, Cent Afr Republ
[6] Fac Sci Sante, SIDA, Bangui, Cent Afr Republ
[7] Ctr Natl Reference Malad Sexuellement Transmissib, Bangui, Cent Afr Republ
关键词
D O I
10.1128/JCM.00113-07
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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-naive 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-naive, 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.
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页码:1838 / 1842
页数:5
相关论文
共 17 条
[1]   Independent levels of cell-free and cell-associated human immunodeficiency virus-1 in genital-tract secretions of clinically asymptomatic, treatment-naive African women [J].
Andréoletti, L ;
Chomont, N ;
Grésenguet, G ;
Matta, M ;
Longo, JD ;
Carreno, MP ;
Si-Mohamed, A ;
Legoff, J ;
Kazatchkine, MD ;
Bélec, L .
JOURNAL OF INFECTIOUS DISEASES, 2003, 188 (04) :549-554
[2]  
[Anonymous], 1992, MacClade: Analysis of phylogeny and character evolution
[3]  
BELEC L, 1995, CLIN DIAGN LAB IMMUN, V2, P57
[4]   Recent observations on HIV type-1 infection in the genital tract of men and women [J].
Coombs, RW ;
Reichelderfer, PS ;
Landay, AL .
AIDS, 2003, 17 (04) :455-480
[5]   Cellular replication of human immunodeficiency virus type 1 occurs in vaginal secretions [J].
Ellerbrock, TV ;
Lennox, JL ;
Clancy, KA ;
Schinazi, RF ;
Wright, TC ;
Pratt-Palmore, M ;
Evans-Strickfaden, T ;
Schnell, C ;
Pai, R ;
Conley, LJ ;
Parrish-Kohler, EE ;
Bush, TJ ;
Tatti, K ;
Hart, CE .
JOURNAL OF INFECTIOUS DISEASES, 2001, 184 (01) :28-36
[6]   HIV-1 in genital tract and plasma of women: Compartmentalization of viral sequences, coreceptor usage, and glycosylation [J].
Kemal, KS ;
Foley, B ;
Burger, H ;
Anastos, K ;
Minkoff, H ;
Kitchen, C ;
Philpott, SM ;
Gao, W ;
Robison, E ;
Holman, S ;
Dehner, C ;
Beck, S ;
Meyer, WA ;
Landay, A ;
Kovacs, A ;
Bremer, J ;
Weiser, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (22) :12972-12977
[7]   Determinants for sensitivity of human immunodeficiency virus coreceptor CXCR4 to the bicyclam AMD3100 [J].
Labrosse, B ;
Brelot, A ;
Heveker, N ;
Sol, N ;
Schols, D ;
De Clercq, E ;
Alizon, M .
JOURNAL OF VIROLOGY, 1998, 72 (08) :6381-6388
[8]   INTRAHOST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EVOLUTION IS RELATED TO LENGTH OF THE IMMUNOCOMPETENT PERIOD [J].
LUKASHOV, VV ;
KUIKEN, CL ;
GOUDSMIT, J .
JOURNAL OF VIROLOGY, 1995, 69 (11) :6911-6916
[9]   Interactions between herpes simplex virus type 2 and human immunodeficiency virus type 1 infection in African women:: Opportunities for intervention [J].
Mbopi-Kéou, FX ;
Grésenguet, G ;
Mayaud, P ;
Weiss, HA ;
Gopal, R ;
Matta, M ;
Paul, JL ;
Brown, DWG ;
Hayes, RJ ;
Mabey, DCW ;
Bélec, L .
JOURNAL OF INFECTIOUS DISEASES, 2000, 182 (04) :1090-1096
[10]   Importance and detection of virus reservoirs and compartments of HIV infection [J].
Nickle, DC ;
Shriner, D ;
Mittler, JE ;
Frenkel, LM ;
Mullins, JI .
CURRENT OPINION IN MICROBIOLOGY, 2003, 6 (04) :410-416