title: Dynamics of envelope evolution in clade C SHIV-infected pig-tailed macaques during disease progression analyzed by ultra-deep pyrosequencing.
abstract: Understanding the evolution of the human immunodeficiency virus type 1 (HIV-1) envelope during disease progression can provide tremendous insights for vaccine development, and simian-human immunodeficiency virus (SHIV) infection of non-human primate provides an ideal platform for such studies. A newly developed clade C SHIV, SHIV-1157ipd3N4, which was able to infect rhesus macaques, closely resembled primary HIV-1 in transmission and pathogenesis, was used to infect several pig-tailed macaques. One of the infected animals subsequently progressed to AIDS, whereas one remained a non-progressor. The viral envelope evolution in the infected animals during disease progression was analyzed by a bioinformatics approach using ultra-deep pyrosequencing. Our results showed substantial envelope variations emerging in the progressor animal after the onset of AIDS. These envelope variations impacted the length of the variable loops and charges of different envelope regions. Additionally, multiple mutations were located at the CD4 and CCR5 binding sites, potentially affecting receptor binding affinity, viral fitness and they might be selected at late stages of disease. More importantly, these envelope mutations are not random since they had repeatedly been observed in a rhesus macaque and a human infant infected by either SHIV or HIV-1, respectively, carrying the parental envelope of the infectious molecular clone SHIV-1157ipd3N4. Moreover, similar mutations were also observed from other studies on different clades of envelopes regardless of the host species. These recurring mutations in different envelopes suggest that there may be a common evolutionary pattern and selection pathway for the HIV-1 envelope during disease progression.
authors.affiliation: Nebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: For Yue
authors.initials: FY
authors.lastname: Tso
authors.forename: Damien C
authors.initials: DC
authors.lastname: Tully
authors.forename: Sandra
authors.initials: S
authors.lastname: Gonzalez
authors.forename: Christopher
authors.initials: C
authors.lastname: Quince
authors.forename: On
authors.initials: O
authors.lastname: Ho
authors.forename: Patricia
authors.initials: P
authors.lastname: Polacino
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
authors.forename: Shiu-Lok
authors.initials: SL
authors.lastname: Hu
authors.forename: Charles
authors.initials: C
authors.lastname: Wood
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D018450:Disease Progression; D019143:Evolution, Molecular; D014644:Genetic Variation; D015497:HIV-1 / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D008254:Macaca nemestrina; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D019713:Receptors, CCR5 / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D019713:Receptors, CCR5; D014759:Viral Envelope Proteins