Adaptive changes after human immunodeficiency virus type 1 transmission.
Primary HIV-1 infection (PHI) is associated with a period of viremia, the resolution of which generally coincides with the development of both humoral and cellular immune responses. In this study replication-competent quasispecies were derived from virus isolated from an individual before and after seroconversion. Virus was also isolated from the presumed donor. Phenotypic and genotypic analysis of biological clones identified transmission of an R5/M-tropic phenotype. However, the ability of clones derived from the recipient to replicate in primary macrophages and PBMCs was restricted after transmission. This apparent selection process was supported by analysis of molecular clones derived from the isolated virus. Analysis of the ratio of synonymous and nonsynonymous substitutions predicted the existence of selective pressure soon after transmission, coincident with the development of HIV-1-specific antibodies. An Env trans-complementation assay demonstrated that the infectivity of a clone derived from the recipient after seroconversion was enhanced in the presence of a selected neutralizing antibody, indicating that the developing humoral immune response may have at least in part contributed to the selective pressure identified.
Lawson
Victoria A
VA
AIDS Cellular Biology Unit and National Centre in HIV Virology Research, Macfarlane Burnet Institute for Medical Research and Public Health, Fairfield, Melbourne, Victoria, Australia 3078. vlawson@niad.nih.gov
Oelrichs
Robert
R
Guillon
Christophe
C
Imrie
Allison A
AA
Cooper
David A
DA
Deacon
Nicholas J
NJ
McPhee
Dale A
DA
D000222:Adaptation, Physiological; D001483:Base Sequence; D017931:DNA Primers; D015752:Genes, env; D005816:Genetic Complementation Test; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D014774:Virulence; D014779:Virus Replication
D017931:DNA Primers; D015483:HIV Antibodies