title: Simian immunodeficiency virus variants with differential T-cell and macrophage tropism use CCR5 and an unidentified cofactor expressed in CEMx174 cells for efficient entry.
abstract: The recent identification of coreceptors that mediate efficient entry of human immunodeficiency virus type 1 (HIV-1) suggests new therapeutic and preventive strategies. We analyzed simian immunodeficiency virus (SIV) entry cofactors to investigate whether the macaque SIV model can be used as an experimental model to evaluate these strategies. Similar to primary HIV-1 isolates, a well-characterized molecular clone, SIVmac239, which replicates poorly but efficiently enters into rhesus alveolar macrophages and an envelope variant, SIVmac239/316Env, with an approximately 1,000-fold-higher replicative capacity in macrophages used the beta-chemokine receptor CCR5 for efficient entry. The transmembrane portion of 316Env allowed low-level entry into cells expressing CCR1, CCR2B, and CCR3. A single amino acid substitution in the V3 loop of SIVmac239/316Env, 321P-->S, impaired the ability to enter into the T-B hybrid cell line CEMx174 but had relatively little effect on entry into primary cells and HOS.CD4 cells expressing CCR5. Although CEMx174 cells do not express CCR5, most SIVmac variants entered this hybrid cell line efficiently but did not enter the parental T-cell line CEM. It seems likely that CEMx174 cells express an as-yet-unidentified, perhaps B-cell-derived cofactor which allows efficient entry of SIVmac.
authors.affiliation: Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, Germany. fkkirchh@viro.med.uni-erlangen.de
authors.forename: F
authors.initials: F
authors.lastname: Kirchhoff
authors.forename: S
authors.initials: S
authors.lastname: Pöhlmann
authors.forename: M
authors.initials: M
authors.lastname: Hamacher
authors.forename: R E
authors.initials: RE
authors.lastname: Means
authors.forename: T
authors.initials: T
authors.lastname: Kraus
authors.forename: K
authors.initials: K
authors.lastname: Uberla
authors.forename: P
authors.initials: P
authors.lastname: Di Marzio
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D002460:Cell Line; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000821:virology*; D008561:Membrane Fusion; D008562:Membrane Glycoproteins; D011392:Proline / Q000378:metabolism; D019713:Receptors, CCR5; D018121:Receptors, Cytokine / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D014759:Viral Envelope Proteins; D014779:Virus Replication
chemical_list: D001685:Biological Factors; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus; D012694:Serine; D011392:Proline