title: Human immunodeficiency virus type 1 replication in dendritic cell-T-cell cocultures is increased upon incorporation of host LFA-1 due to higher levels of virus production in immature dendritic cells.
abstract: Dendritic cells (DCs) act as a portal for invasion by human immunodeficiency virus type-1 (HIV-1). Here, we investigated whether virion-incorporated host cell membrane proteins can affect virus replication in DC-T-cell cocultures. Using isogenic viruses either devoid of or bearing host-derived leukocyte function-associated antigen 1 (LFA-1), we showed that HIV-1 production is augmented when LFA-1-bearing virions are used compared to that for viral entities lacking this adhesion molecule. This phenomenon was observed in immature monocyte-derived DCs (IM-MDDCs) only and not in DCs displaying a mature phenotype. The increase is not due to higher virus production in responder CD4(+) T cells but rather is linked with a more important productive infection of IM-MDDCs. We provided evidence that virus-associated host LFA-1 molecules do not affect a late event in the HIV-1 life cycle but rather exert an effect on an early step in virus replication. We demonstrated that the enhancement of productive infection of IM-MDDCs that is conferred by virus-anchored host LFA-1 involves the protein kinase A (PKA) and PKC signal transduction pathways. The biological significance of this phenomenon was established by performing experiments with virus stocks produced in primary human cells and anti-LFA-1 antibodies. Together, our results indicate that the association between some virus-bound host proteins and their natural cognate ligands can modulate de novo HIV-1 production by IM-MDDCs. Therefore, the additional interactions between virus-bound host cell membrane constituents and counter receptors on the surfaces of DCs can influence HIV-1 replication in IM-MDDC-T-cell cocultures.
authors.affiliation: Research Center in Infectious Diseases, Laval Univeristy, Quebec, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gilbert
authors.forename: Réjean
authors.initials: R
authors.lastname: Cantin
authors.forename: Corinne
authors.initials: C
authors.lastname: Barat
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D001483:Base Sequence; D018920:Coculture Techniques; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017931:DNA Primers; D003713:Dendritic Cells / Q000821:virology*; D004197:Disease Reservoirs; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D014779:Virus Replication / Q000502:physiology*
chemical_list: D017931:DNA Primers; D016169:Lymphocyte Function-Associated Antigen-1; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C