title: Neuraminidase from a bacterial source enhances both HIV-1-mediated syncytium formation and the virus binding/entry process.
abstract: Neuraminidases, also termed sialidases, which catalyze the removal of sialic acid residues from various glycoconjugates, have been previously reported to modulate HIV-1 replication. Given that some of the known opportunistic microbes found in patients infected with HIV-1 harbor neuraminidase (NA) activity, we speculated that pathogen-derived NA might be envisaged as an important factor in the pathogenesis of this retroviral infection. In the present study, we have monitored the putative modulation of HIV-1-mediated syncytium formation and virus replication by highly purified bacterial-derived NA from Arthrobacter ureafaciens. Taking advantage of a luciferase-based syncytium quantitative assay, we demonstrate here that the level of HIV-1-mediated syncytium formation is enhanced in the presence of NA and that it necessitates interaction between gp120 and CD4/chemokine coreceptor. By using pseudotyped recombinant luciferase-encoding HIV-1 particles, we found that NA treatment of human CD4-positive target cells (i.e., T lymphoid, monocytoid, and peripheral blood mononuclear cells) significantly augmented single-round infection by T- and macrophage-tropic isolates of HIV-1. The observed increase in HIV-1 infection was linked with an enhancement in the initial steps of the virus replicative cycle as monitored by viral binding and entry assays. Interestingly, NA treatment also enhances infectivity of HIV-1 pseudotypes with envelope glycoprotein from the amphotropic murine leukemia virus or the vesicular stomatitis virus. Taken together, our results provide useful information regarding the possible contribution of microbial agents carrying NA activity to HIV-1 pathogenesis.
authors.affiliation: Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: B
authors.initials: B
authors.lastname: Barbeau
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: M J
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D001173:Arthrobacter / Q000201:enzymology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018920:Coculture Techniques; D015726:Giant Cells / Q000821:virology*; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism*; D011991:Receptors, Virus / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000378:metabolism; D014771:Virion / Q000378:metabolism; D014779:Virus Replication
chemical_list: C028391:G protein, vesicular stomatitis virus; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid