title: Viral genetic evolution in macaques infected with molecularly cloned simian immunodeficiency virus correlates with the extent of persistent viremia.
abstract: Genetic evolution of the simian immunodeficiency virus (SIV) envelope glycoprotein was evaluated in a group of six macaques (Macaca nemestrina) infected with the molecularly cloned, moderately pathogenic SIVsm62d. The extent of envelope evolution was subsequently evaluated within the context of the individual pattern of viremia and disease outcome. Two macaques in this cohort developed AIDS by 1.5 years postinoculation (progressors), whereas the remaining four macaques remained asymptomatic (nonprogressors). Compared with the nonprogressor macaques, the two progressor macaques exhibited higher persistent plasma viremia, higher homologous neutralizing antibody titers, and more extensive mutation and evolution in the V1 region of envelope. Although clearly distinct in each of these parameters from the progressors, the four nonprogressors exhibited more individual variability with respect to the extent of persistent viremia and genetic evolution of the V1 region of envelope. The extent of V1 envelope varied from no apparent V1 evolution in a macaque with good viral containment to extensive evolution in one macaque with persistent viremia. This study underscores the critical role of persistent replication in the genetic evolution of SIV.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Twinbrook II Facility, Rockville, Maryland 20852, USA. vhirsch@atlas.niaid.nih.gov
authors.forename: V M
authors.initials: VM
authors.lastname: Hirsch
authors.forename: G
authors.initials: G
authors.lastname: Dapolito
authors.forename: A
authors.initials: A
authors.lastname: Hahn
authors.forename: J
authors.initials: J
authors.lastname: Lifson
authors.forename: D
authors.initials: D
authors.lastname: Montefiori
authors.forename: C R
authors.initials: CR
authors.lastname: Brown
authors.forename: R
authors.initials: R
authors.lastname: Goeken
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D005075:Biological Evolution; D018450:Disease Progression; D007963:Leukocytes, Mononuclear / Q000821:virology; D008254:Macaca nemestrina; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017386:Sequence Homology, Amino Acid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000503:physiopathology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology; D014766:Viremia
chemical_list: D000914:Antibodies, Viral