title: Identification and characterization of a macrophage-tropic SIV envelope glycoprotein variant in blood from early infection in SIVmac251-infected macaques.
abstract: Macrophages play an important role in HIV/SIV pathogenesis by serving as a reservoir for viral persistence in brain and other tissues. Infected macrophages have been detected in brain early after infection, but macrophage-tropic viruses are rarely isolated until late-stage infection. Little is known about early variants that establish persistent infection in brain. Here, we characterize a unique macrophage-tropic SIV envelope glycoprotein (Env) variant from two weeks post-infection in blood of an SIVmac251-infected macaque that is closely related to sequences in brain from animals with neurological disease. SIVmac251 clones expressing this Env are highly fusogenic, and replicate efficiently in T cells and macrophages. N173 and N481 were identified as novel determinants of macrophage tropism and neutralization sensitivity. These results imply that macrophage-tropic SIV capable of establishing viral reservoirs in brain can be present in blood during early infection. Furthermore, these SIVmac251 clones will be useful for studies on pathogenesis, eradication, and vaccines.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Medical Sciences Program in Virology, Harvard Medical School, Boston, MA, USA.
authors.forename: Po-Jen
authors.initials: PJ
authors.lastname: Yen
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Medical Sciences Program in Virology, Harvard Medical School, Boston, MA, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Mefford
authors.affiliation: Department of Medicine, Hematology-Oncology Division, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Hoxie
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, USA.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Williams
authors.affiliation: New England Primate Research Center, Department of Microbiology and Immunobiology, Harvard Medical School, Southborough, MA, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Desrosiers
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA. Electronic address: Dana_Gabuzda@dfci.harvard.edu.
authors.forename: Dana
authors.initials: D
authors.lastname: Gabuzda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015967:Gene Expression Regulation, Viral; D014644:Genetic Variation; D057809:HEK293 Cells; D006801:Humans; D008253:Macaca mulatta; D008264:Macrophages / Q000821:virology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000145:classification* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
chemical_list: D014759:Viral Envelope Proteins
keywords: Brain; Envelope glycoprotein (Env); Human immunodeficiency virus (HIV); Macrophage tropism; Simian immunodeficiency virus (SIV)