The influence of CD4 and CXCR4 on maedi-visna virus-induced syncytium formation.
CD4 is the principal binding site for human and simian immunodeficiency virus (HIV/SIV) receptor interactions and the a chemokine receptor CXCR4 has been implicated as a primordial lentivirus receptor. This study sought to determine the relevance of CD4 and CXCR4 in virus-receptor interactions for the prototype lentivirus, maedi-visna virus (MVV) of sheep. Neither CD4 nor alpha/beta chemokine receptors represent principal receptors for MVV since human osteosarcoma cells devoid of these molecules were susceptible to productive infection. Interestingly, the presence of either CD4 and/or CXCR4 on indicator cells dramatically enhanced MVV-induced cell fusion (syncytium formation) for three independent virus strains. Syncytium formation results from virus-receptor interactions and can be inhibited by receptor ligands. However, neither SDF-la that binds CXCR4 nor recombinant gp120 (rgp120) that binds CD4 could specifically inhibit the observed enhancement of MVV-induced cell fusion under conditions that significantly reduced HIV-1-induced cell fusion. Our observations suggest that CD4 and CXCR4 may represent optional auxiliary components of an MVV receptor (or receptor complex) that facilitate MVV-mediated membrane fusion events, a feature important for virus entry. This potential accessory role for CXCR4 in MW receptor interactions may reflect the distant relationship between the ovine (MVV) and the human/feline lentiviruses (HIV/FIV).
Hovden
Arnt-Ove
AO
Department of Molecular Biology, The Gade Institute, University of Bergen, Bergen High Technology Centre, Bergen, Norway.
Sommerfelt
Maja A
MA
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015726:Giant Cells / Q000276:immunology* / Q000821:virology*; D006801:Humans; D008969:Molecular Sequence Data; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012756:Sheep; D014790:Visna-maedi virus / Q000276:immunology* / Q000472:pathogenicity*
D015704:CD4 Antigens; D019718:Receptors, CXCR4; D011991:Receptors, Virus