PMID- 17494076 OWN - NLM STAT- MEDLINE DCOM- 20070914 LR - 20181113 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 81 IP - 14 DP - 2007 Jul TI - 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. PG - 7672-82 AB - 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. FAU - Gilbert, Caroline AU - Gilbert C AD - Research Center in Infectious Diseases, Laval Univeristy, Quebec, Canada. FAU - Cantin, Rejean AU - Cantin R FAU - Barat, Corinne AU - Barat C FAU - Tremblay, Michel J AU - Tremblay MJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070509 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (DNA Primers) RN - 0 (Lymphocyte Function-Associated Antigen-1) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - Base Sequence MH - Coculture Techniques MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - DNA Primers MH - Dendritic Cells/*virology MH - Disease Reservoirs MH - HIV-1/*physiology MH - Humans MH - Lymphocyte Function-Associated Antigen-1/*physiology MH - Polymerase Chain Reaction MH - Protein Kinase C/metabolism MH - Signal Transduction MH - Virus Replication/*physiology PMC - PMC1933380 EDAT- 2007/05/12 09:00 MHDA- 2007/09/15 09:00 PMCR- 2007/11/01 CRDT- 2007/05/12 09:00 PHST- 2007/05/12 09:00 [pubmed] PHST- 2007/09/15 09:00 [medline] PHST- 2007/05/12 09:00 [entrez] PHST- 2007/11/01 00:00 [pmc-release] AID - JVI.02810-06 [pii] AID - 2810-06 [pii] AID - 10.1128/JVI.02810-06 [doi] PST - ppublish SO - J Virol. 2007 Jul;81(14):7672-82. doi: 10.1128/JVI.02810-06. Epub 2007 May 9.