title: Differential coreceptor expression allows for independent evolution of non-syncytium-inducing and syncytium-inducing HIV-1.
abstract: We demonstrated previously that CD45RA(+) CD4(+) T cells are infected primarily by syncytium-inducing (SI) HIV-1 variants, whereas CD45RO(+) CD4(+) T cells harbor both non-SI (NSI) and SI HIV-1 variants. Here, we studied evolution of tropism for CD45RA(+) and CD45RO(+) CD4(+) cells, coreceptor usage, and molecular phylogeny of coexisting NSI and SI HIV-1 clones that were isolated from four patients in the period spanning SI conversion. NSI variants were CCR5-restricted and could be isolated throughout infection from CD45RO(+) CD4(+) cells. SI variants seemed to evolve in CD45RO(+) CD4(+) cells, but, in time, SI HIV-1 infection of CD45RA(+) CD4(+) cells equaled infection of CD45RO(+) CD4(+) cells. In parallel with this shift, SI HIV-1 variants first used both coreceptors CCR5 and CXCR4, but eventually lost the ability to use CCR5. Phylogenetically, NSI and SI HIV-1 populations diverged over time. We observed a differential expression of HIV-1 coreceptors within CD45RA(+) and CD45RO(+) cells, which allowed us to isolate virus from purified CCR5(+) CXCR4(-) and CCR5(-) CXCR4(+) CD4(+) cells. The CCR5(+) subset was exclusively infected by CCR5-dependent HIV-1 clones, whereas SI clones were preferentially isolated from the CXCR4(+) subset. The differential expression of HIV-1 coreceptors provides distinct cellular niches for NSI and SI HIV-1, contributing to their coexistence and independent evolutionary pathways.
authors.affiliation: Department of Clinical Viro-Immunology, CLB Sanquin and Laboratory of Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: R P
authors.initials: RP
authors.lastname: van Rij
authors.forename: H
authors.initials: H
authors.lastname: Blaak
authors.forename: J A
authors.initials: JA
authors.lastname: Visser
authors.forename: M
authors.initials: M
authors.lastname: Brouwer
authors.forename: R
authors.initials: R
authors.lastname: Rientsma
authors.forename: S
authors.initials: S
authors.lastname: Broersen
authors.forename: A M
authors.initials: AM
authors.lastname: de Roda Husman
authors.forename: H
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000821:virology*; D019143:Evolution, Molecular; D014644:Genetic Variation; D015726:Giant Cells / Q000821:virology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D017493:Leukocyte Common Antigens; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D010641:Phenotype; D010802:Phylogeny; D019713:Receptors, CCR5 / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics; D015728:Receptors, HIV / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D016176:T-Lymphocyte Subsets / Q000821:virology
chemical_list: D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D017493:Leukocyte Common Antigens