HIV-2 infects resting CD4+ T cells but not monocyte-derived dendritic cells

Retrovirology

Olivier Schwartz³  Diane Descamps⁴  Benoit Visseaux⁴  Daniela Bruni⁵  Françoise Porrot²  Ferdinand Roesch¹  Diana Ayinde²  Isabel Puigdomenech²  Lise Chauveau¹ 

[1] Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris 75015, France;Institut Pasteur, URA CNRS 3015, Virus & Immunity Unit, Paris, France;Vaccine Research Institute, Hôpital Henri Mondor, Créteil, France;AP-HP, Hôpital Bichat, Laboratoire de Virologie, Paris, France;Institut Pasteur, Hepacivirus & Innate Immunity Unit, Paris, France

关键词: Interferon;    CD4+ lymphocytes;    Monocyte-derived dendritic cells;    SAMHD1;    Vpx;    HIV-2;   

Others  :  1132001
DOI  :  10.1186/s12977-014-0131-7

 received in 2014-11-18, accepted in 2014-12-17,  发布年份 2015

【 摘 要 】

Background

Human Immunodeficiency Virus-type 2 (HIV-2) encodes Vpx that degrades SAMHD1, a cellular restriction factor active in non-dividing cells. HIV-2 replicates in lymphocytes but the susceptibility of monocyte-derived dendritic cells (MDDCs) to in vitro infection remains partly characterized.

Results

Here, we investigated HIV-2 replication in primary CD4+ T lymphocytes, both activated and non-activated, as well as in MDDCs. We focused on the requirement of Vpx for productive HIV-2 infection, using the reference HIV-2 ROD strain, the proviral clone GL-AN, as well as two primary HIV-2 isolates. All HIV-2 strains tested replicated in activated CD4+ T cells. Unstimulated CD4+ T cells were not productively infected by HIV-2, but viral replication was triggered upon lymphocyte activation in a Vpx-dependent manner. In contrast, MDDCs were poorly infected when exposed to HIV-2. HIV-2 particles did not potently fuse with MDDCs and did not lead to efficient viral DNA synthesis, even in the presence of Vpx. Moreover, the HIV-2 strains tested were not efficiently sensed by MDDCs, as evidenced by a lack of MxA induction upon viral exposure. Virion pseudotyping with VSV-G rescued fusion, productive infection and HIV-2 sensing by MDDCs.

Conclusion

Vpx allows the non-productive infection of resting CD4+ T cells, but does not confer HIV-2 with the ability to efficiently infect MDDCs. In these cells, an entry defect prevents viral fusion and reverse transcription independently of SAMHD1. We propose that HIV-2, like HIV-1, does not productively infect MDDCs, possibly to avoid triggering an immune response mediated by these cells.

【 授权许可】

   
2015 Chauveau et al.; licensee BioMed Central.

【 图 表 】

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