title: Highly pathogenic simian immunodeficiency virus mne variants that emerge during the course of infection evolve enhanced infectivity and the ability to downregulate CD4 but not class I major histocompatibility complex antigens.
abstract: The replicative, cytopathic, and antigenic properties of simian immunodeficiency virus (SIV) variants influence its replication efficiency in vivo. To further define the viral properties and determinants that may be important for high-level replication in vivo and progression to AIDS, we compared a minimally pathogenic SIVmne molecular clone with two highly pathogenic variants cloned from late stages of infection. Both variants had evolved greater infectivity than the parental clone due to mutations in nef. Interestingly, a pol determinant in one of the highly pathogenic variants also contributed to its increased infectivity. Furthermore, because replication in vivo may also be influenced by the ability of a virus to evade the cellular immune response of the host, we examined whether the variants were more capable of downregulating surface expression of class I major histocompatibility complex (MHC). Decreased MHC class I expression was not observed in cells infected with any of the viruses. Furthermore, the Nef proteins of the highly pathogenic variants only slightly reduced surface MHC class I expression in transfected cells, although they efficiently downregulated CD4. Together, these data demonstrate that mutations which can enhance viral infectivity, as well as CD4 downregulation, may be important for efficient replication of SIV in the host. However, Nef-mediated reduction of MHC class I expression does not appear to be critical for the increased in vivo replicative ability of highly pathogenic late variants.
authors.affiliation: Department of Virology and Immunology, Southwest Foundation for Biomedical Research, 7620 NW Loop 410 @ Military Drive, San Antonio, TX 78227, USA.
authors.forename: Parul G
authors.initials: PG
authors.lastname: Patel
authors.forename: Monica T
authors.initials: MT
authors.lastname: Yu Kimata
authors.forename: Julia E
authors.initials: JE
authors.lastname: Biggins
authors.forename: Joelle M
authors.initials: JM
authors.lastname: Wilson
authors.forename: Jason T
authors.initials: JT
authors.lastname: Kimata
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D015693:Gene Products, nef / Q000737:chemistry / Q000502:physiology; D014644:Genetic Variation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008254:Macaca nemestrina; D008969:Molecular Sequence Data; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D014779:Virus Replication
chemical_list: D015704:CD4 Antigens; D015693:Gene Products, nef; D015395:Histocompatibility Antigens Class I