title: Gp120 V3-dependent impairment of R5 HIV-1 infectivity due to virion-incorporated CCR5.
abstract: Entry of R5 human immunodeficiency virus type 1 (HIV-1) into target cells requires sequential interactions of the envelope glycoprotein gp120 with the receptor CD4 and the coreceptor CCR5. We investigated replication of 45 R5 viral clones derived from the HIV-1JR-FLan library carrying 0-10 random amino acid substitutions in the gp120 V3 loop. It was found that 6.7% (3/45) of the viruses revealed >or=10-fold replication suppression in PM1/CCR5 cells expressing high levels of CCR5 compared with PM1 cells expressing low levels of CCR5. In HIV-1V3L#08, suppression of replication was not associated with entry events and viral production but with a marked decrease in infectivity of nascent progeny virus. HIV-1V3L#08, generated from infected PM1/CCR5 cells, was 98% immunoprecipitated by anti-CCR5 monoclonal antibody T21/8, whereas the other infectious viruses were only partially precipitated, suggesting that incorporation of larger amounts of CCR5 into the virions caused impairment of viral infectivity in HIV-1V3L#08. The results demonstrate the implications of an alternative influence of CCR5 on HIV-1 replication.
authors.affiliation: Department of Medical Virology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Monde
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Maeda
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Shinji
authors.initials: S
authors.lastname: Harada
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yusa
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D020125:Mutation, Missense; D017433:Protein Structure, Secondary; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization; D014779:Virus Replication / Q000502:physiology
chemical_list: D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; C514793:gp120 protein, Human immunodeficiency virus 1