title: Comparison of viral Env proteins from acute and chronic infections with subtype C human immunodeficiency virus type 1 identifies differences in glycosylation and CCR5 utilization and suggests a new strategy for immunogen design.
abstract: Understanding human immunodeficiency virus type 1 (HIV-1) transmission is central to developing effective prevention strategies, including a vaccine. We compared phenotypic and genetic variation in HIV-1 env genes from subjects in acute/early infection and subjects with chronic infections in the context of subtype C heterosexual transmission. We found that the transmitted viruses all used CCR5 and required high levels of CD4 to infect target cells, suggesting selection for replication in T cells and not macrophages after transmission. In addition, the transmitted viruses were more likely to use a maraviroc-sensitive conformation of CCR5, perhaps identifying a feature of the target T cell. We confirmed an earlier observation that the transmitted viruses were, on average, modestly underglycosylated relative to the viruses from chronically infected subjects. This difference was most pronounced in comparing the viruses in acutely infected men to those in chronically infected women. These features of the transmitted virus point to selective pressures during the transmission event. We did not observe a consistent difference either in heterologous neutralization sensitivity or in sensitivity to soluble CD4 between the two groups, suggesting similar conformations between viruses from acute and chronic infection. However, the presence or absence of glycosylation sites had differential effects on neutralization sensitivity for different antibodies. We suggest that the occasional absence of glycosylation sites encoded in the conserved regions of env, further reduced in transmitted viruses, could expose specific surface structures on the protein as antibody targets.
authors.affiliation: UNC Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Ping
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Joseph
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Anderson
authors.forename: Melissa-Rose
authors.initials: MR
authors.lastname: Abrahams
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Salazar-Gonzalez
authors.forename: Laura P
authors.initials: LP
authors.lastname: Kincer
authors.forename: Florette K
authors.initials: FK
authors.lastname: Treurnicht
authors.forename: Leslie
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authors.lastname: Arney
authors.forename: Suany
authors.initials: S
authors.lastname: Ojeda
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Jessica
authors.initials: J
authors.lastname: Keys
authors.forename: E Lake
authors.initials: EL
authors.lastname: Potter
authors.forename: Haitao
authors.initials: H
authors.lastname: Chu
authors.forename: Penny
authors.initials: P
authors.lastname: Moore
authors.forename: Maria G
authors.initials: MG
authors.lastname: Salazar
authors.forename: Shilpa
authors.initials: S
authors.lastname: Iyer
authors.forename: Cassandra
authors.initials: C
authors.lastname: Jabara
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kirchherr
authors.forename: Clement
authors.initials: C
authors.lastname: Mapanje
authors.forename: Nobubelo
authors.initials: N
authors.lastname: Ngandu
authors.forename: Cathal
authors.initials: C
authors.lastname: Seoighe
authors.forename: Irving
authors.initials: I
authors.lastname: Hoffman
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Tang
authors.forename: Celia
authors.initials: C
authors.lastname: Labranche
authors.forename: Benhur
authors.initials: B
authors.lastname: Lee
authors.forename: Andrew
authors.initials: A
authors.lastname: Saville
authors.forename: Marion
authors.initials: M
authors.lastname: Vermeulen
authors.forename: Susan
authors.initials: S
authors.lastname: Fiscus
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Salim Abdool
authors.initials: SA
authors.lastname: Karim
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Myron S
authors.initials: MS
authors.lastname: Cohen
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.forename: Ronald
authors.initials: R
authors.lastname: Swanstrom
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006031:Glycosylation; D015658:HIV Infections / Q000378:metabolism* / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008295:Malawi; D008297:Male; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010802:Phylogeny; D011487:Protein Conformation; D019713:Receptors, CCR5 / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D013019:South Africa; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology
chemical_list: D019713:Receptors, CCR5; D014759:Viral Envelope Proteins