title: Vaccination reduces simian-human immunodeficiency virus sequence reversion through enhanced viral control.
abstract: It has been suggested that vaccination prior to infection may direct the mutational evolution of human immunodeficiency virus type 1 (HIV-1) to a less fit virus, resulting in an attenuated course of disease. The present study was initiated to explore whether prior immunization might prevent the reversion of the virus to the wild-type form. Mamu-A*01 monkeys were vaccinated to generate a cytotoxic T-lymphocyte response to the immunodominant Gag p11C epitope and were then challenged with a cloned pathogenic CXCR4-tropic simian-human immunodeficiency virus (SHIV) expressing a mutant Gag p11C sequence (Δp11C SHIV). The epitopic and extraepitopic compensatory mutations introduced into gag of Δp11C SHIV resulted in attenuated replicative capacity and eventual reversions to the wild-type Gag p11C sequence in naïve rhesus monkeys. However, in vaccinated rhesus monkeys, no reversions of the challenge virus were observed, an effect that may have been a consequence of significantly decreased viral replication rather than a redirection of the mutational evolution of the virus. These findings highlight the multifactorial pressures that affect the evolution of primate immunodeficiency viruses.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Manuel
authors.forename: Wendy W
authors.initials: WW
authors.lastname: Yeh
authors.forename: Harikrishnan
authors.initials: H
authors.lastname: Balachandran
authors.forename: Ryon H
authors.initials: RH
authors.lastname: Clarke
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lifton
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D015683:Gene Products, gag / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D017354:Point Mutation; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018449:SAIDS Vaccines / Q000627:therapeutic use*; D017386:Sequence Homology, Amino Acid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D014611:Vaccination; D019562:Viral Load; D014779:Virus Replication / Q000235:genetics*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; D012333:RNA, Messenger; D018449:SAIDS Vaccines