title: Although macrophage-tropic simian/human immunodeficiency viruses can exhibit a range of pathogenic phenotypes, a majority of isolates induce no clinical disease in immunocompetent macaques.
abstract: Unlike prototypical lentiviruses like visna and caprine arthritis-encephalitis viruses, which are mainly macrophage tropic (M-tropic), primate lentiviruses primarily target CD4+ T lymphocytes. We previously reported that during the late phase of highly pathogenic chimeric simian/human immunodeficiency virus (SHIV) infections of rhesus macaques, when CD4+ T cells have been systemically eliminated, high levels of viremia are maintained from productively infected macrophages. The availability of several different M-tropic SHIVs from such late-stage immunocompromised animals provided the opportunity to assess whether they might contribute to the immune deficiency induced by their T-cell-tropic parental viruses or possibly cause a distinct disease based on their capacity to infect macrophages. Pairs of rhesus monkeys were therefore inoculated intravenously with six different M-tropic SHIV preparations, and their plasma viral RNA loads, circulating lymphocyte subset numbers, and eventual disease outcomes were monitored. Only one of these six M-tropic SHIVs induced any disease; the disease phenotype observed was the typical rapid, complete, and irreversible depletion of CD4+ T cells induced by pathogenic SHIVs. An analysis of two asymptomatic monkeys, previously inoculated with an M-tropic SHIV recovered directly from alveolar macrophages, revealed that this inoculum targeted alveolar macrophages in vivo, compared to a T-cell-tropic virus, yet no clinical disease occurred. Although one isolate did, in fact, induce the prototypical rapid, irreversible, and complete loss of CD4+ T cells, indicating that M-tropism and pathogenicity may not be inversely related, the majority of M-tropic SHIVs induced no clinical disease in immunocompetent macaques.
authors.affiliation: Laboratory of Molecular Microbiology, Building 4, Room 315, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Olivia K
authors.initials: OK
authors.lastname: Donau
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imamichi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Theodore
authors.forename: Ranjini
authors.initials: R
authors.lastname: Iyengar
authors.forename: Christopher
authors.initials: C
authors.lastname: Erb
authors.forename: Alicia
authors.initials: A
authors.lastname: Buckler-White
authors.forename: Charles E
authors.initials: CE
authors.lastname: Buckler
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Martin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002678:Chimera; D006678:HIV / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D008253:Macaca mulatta; D016676:Macrophages, Alveolar / Q000821:virology*; D008969:Molecular Sequence Data; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D012367:RNA, Viral