Details

Autor(en) / Beteiligte

• Ananth, Swetha
• Ambiel, Ina
• Schifferdecker, Sandra
• Müller, Thorsten G.
• Wratil, Paul R.
• Mejias-Perez, Ernesto
• Kräusslich, Hans-Georg
• Müller, Barbara
• Keppler, Oliver T.
• Fackler, Oliver T.

Titel

Spatial resolution of HIV-1 post-entry steps in resting CD4 T cells

Ist Teil von

• Cell reports (Cambridge), 2024-03, Vol.43 (3), p.113941-113941, Article 113941

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Quelle

Elektronische Zeitschriftenbibliothek - Freely accessible e-journals

Beschreibungen/Notizen

• Resting CD4 T cells resist productive HIV-1 infection. The HIV-2/simian immunodeficiency virus protein viral accessory protein X (Vpx) renders these cells permissive to infection, presumably by alleviating blocks at cytoplasmic reverse transcription and subsequent nuclear import of reverse-transcription/pre-integration complexes (RTC/PICs). Here, spatial analyses using quantitative virus imaging techniques reveal that HIV-1 capsids containing RTC/PICs are readily imported into the nucleus, recruit the host dependency factor CPSF6, and translocate to nuclear speckles in resting CD4 T cells. Reverse transcription, however, remains incomplete, impeding proviral integration and viral gene expression. Vpx or pharmacological inhibition of the deoxynucleotide triphosphohydrolase (dNTPase) activity of the restriction factor SAM domain and HD domain-containing protein 1 (SAMHD1) increases levels of nuclear reverse-transcribed cDNA and facilitates HIV-1 integration. Nuclear import and intranuclear transport of viral complexes therefore do not pose important blocks to HIV-1 in resting CD4 T cells, and the limitation to reverse transcription by SAMHD1’s dNTPase activity constitutes the main pre-integration block to infection. [Display omitted] •Quantitative virus imaging visualizes HIV-1 post-entry steps in resting CD4 T cells•HIV-1 capsids are readily imported into the nucleus of resting CD4 T cells•A key block to infection exists at the level of reverse transcription•Vpx or an inhibitor of SAMHD1’s dNTPase activity facilitates reverse transcription Ananth et al. employ quantitative virus imaging techniques to spatially analyze how resting CD4 T cells resist productive HIV-1 infection. While nuclear import and intranuclear transport of viral complexes do not restrict HIV-1 in these cells, SAMHD1’s dNTPase activity poses the main pre-integration block to infection by limiting reverse transcription.