HIV-1 infection of DC: evidence for the acquisition of virus particles from infected T cells by antigen uptake mechanism.
Dendritic cells (DC) play a pivotal role in transmission and dissemination of HIV-1. Earlier studies reported that DC present at the site of infection trap virus particles via DC-SIGN and transfer the virus to the interacting naïve T cells. This prompted us to ask the question whether DC could acquire virus from infected T cells during DC-T cell interaction. To address this, we investigated the likely transfer of virus from HIV-1 infected T cells to DC and the underlying mechanisms involved. Results indicate that DC acquire virus from infected T cells via antigen uptake mechanism and this results in infection of DC with expression of proteins directed by viral DNA. Further studies with HIV-1 lacking the Env protein also resulted in infection of DC. The use of antibodies against DC-SIGN and DC-SIGN-R ruled out a role for receptor in the infection of DC. Additional data show that DC infection is directly correlated with the ability of DC to take up antigen from infected T cells. Overall, these studies provide evidence to suggest that HIV-1, besides infecting immune cells, also utilizes immunological mechanism(s) to acquire and disseminate virus.
Venkatachari
Narasimhan J
NJ
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Alber
Sean
S
Watkins
Simon C
SC
Ayyavoo
Velpandi
V
D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003713:Dendritic Cells / Q000821:virology*; D049452:Green Fluorescent Proteins / Q000737:chemistry; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D037181:Lectins, C-Type / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008856:Microscopy, Fluorescence / Q000379:methods; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D049452:Green Fluorescent Proteins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human