title: Comparison of in vivo and in vitro evolution of CCR5 to CXCR4 coreceptor use of primary human immunodeficiency virus type 1 variants.
abstract: During the course of at least 50% of HIV-1 subtype B infections, CCR5-using (R5) viruses evolve towards a CXCR4-using phenotype. To gain insight in the transition from CCR5 to CXCR4 coreceptor use, we investigated whether acquisition of CXCR4 use in vitro of R5 viruses from four patients resembled this process in vivo. R5 variants from only one patient acquired CXCR4 use in vitro. These variants had envelopes with higher V3 charge and higher number of potential N-linked glycosylation sites when compared to R5 variants that failed to gain CXCR4 use in vitro. In this patient, acquisition of CXCR4 use in vitro and in vivo was associated with multiple mutational patterns not necessarily involving the V3 region. However, changes at specific V3 positions were prerequisite for persistence of CXCR4-using variants in vivo, suggesting that positive selection targeting the V3 loop is required for emergence of CXCR4-using variants during natural disease course.
authors.affiliation: Dept of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA) at Academic Medical Center of University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: Edo-Matas
authors.forename: Karel A
authors.initials: KA
authors.lastname: van Dort
authors.forename: Laurentia C
authors.initials: LC
authors.lastname: Setiawan
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
mesh_terms: D002460:Cell Line; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D053585:Virus Attachment
chemical_list: C527276:CXCR4 protein, human; D015686:Gene Products, env; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV