Characterization of human immunodeficiency virus type 1 replication in immature and mature dendritic cells reveals dissociable cis- and trans-infection.
Dendritic cells (DCs) transmit human immunodeficiency virus type 1 (HIV-1) to CD4(+) T cells through the trans- and cis-infection pathways; however, little is known about the relative efficiencies of these pathways and whether they are interdependent. Here we compare cis- and trans-infections of HIV-1 mediated by immature DCs (iDCs) and mature DCs (mDCs), using replication-competent and single-cycle HIV-1. Monocyte-derived iDCs were differentiated into various types of mDCs by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), and CD40 ligand (CD40L). iDCs and CD40L-induced mDCs were susceptible to HIV-1 infection and mediated efficient viral transmission to CD4(+) T cells. Although HIV-1 cis-infection was partially restricted in TNF-alpha-induced mDCs and profoundly blocked in LPS-induced mDCs, these cells efficiently promoted HIV-1 trans-infection of CD4(+) T cells. The postentry restriction of HIV-1 infection in LPS-induced mDCs was identified at the levels of reverse transcription and postintegration, using real-time PCR quantification of viral DNA and integration. Furthermore, nucleofection of DCs with HIV-1 proviral DNA confirmed that impaired gene expression of LPS-induced mDCs was responsible for the postentry restriction of HIV-1 infection. Our results suggest that various DC subsets in vivo may differentially contribute to HIV-1 dissemination via dissociable cis- and trans-infections.
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Chunsheng
C
Dong
Alicia M
AM
Janas
Jian-Hua
JH
Wang
Wendy J
WJ
Olson
Li
L
Wu
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004279:DNA, Viral; D003713:Dendritic Cells / Q000473:pathology / Q000821:virology*; D015658:HIV Infections; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D016662:Virus Integration; D014779:Virus Replication
D004279:DNA, Viral