Link to Pubmed [PMID] – 28077629
J. Virol. 2017 Jan;
Linker of nucleoskeleton and cytoskeleton (LINC) complexes connect the nucleus to the cytoskeleton in eukaryotic cells. We previously reported that overexpression of SUN2, an inner nuclear membrane protein and LINC complex component, inhibits HIV infection between reverse transcription and nuclear import in a capsid-specific manner. We also reported that SUN2 silencing does not modulate HIV infection in several cell lines. Silencing of SUN2 was recently reported to decrease HIV infection of CD4 T cells, an effect suggested to result from modulation of CypA-dependent steps of HIV infection. We confirm here that HIV infection of primary CD4 T cells is compromised in the absence of endogenous SUN2, and we extend these findings to additional viral strains. However, we find that CypA is not required for the decreased infection observed in SUN2 silenced cells, and conversely, that endogenous SUN2 is not required for the well-documented positive modulation of HIV infection by CypA. In contrast, CD4 T cells lacking SUN2 exhibit a considerable defect in proliferative capacity, and display reduced levels of activation markers and decreased viability. Additionally, SUN2-silenced CD4 T cells that do become infected support reduced levels of viral protein expression. Our results demonstrate that SUN2 is required for optimal activation and proliferation of primary CD4 T cells, and suggest that disruption of these processes explains the contribution of endogenous SUN2 to HIV infection in primary lymphocytes.
IMPORTANCE: Linker of nucleoskeleton and cytoskeleton (LINC) complexes connect the nucleus to the cytoskeleton. We previously reported that overexpression of the LINC complex protein SUN2 inhibits HIV infection, by targeting the viral capsid and blocking infection before the virus enters the nucleus. A recent report showed that depletion of endogenous SUN2 in primary CD4 T cells results in decreased HIV infection, and that this involves Cyclophilin A (CypA), a host protein that interacts with the capsid of HIV to promote infection. We confirm that HIV infection is reduced in CD4 T cells lacking SUN2, but we find no role for CypA. Instead, SUN2 silencing results in CD4 T cells with decreased viability and much lower proliferation rates. Our results show that SUN2 is required for optimal CD4 T cell activation and proliferation, and explain the reduced level of HIV infection in the absence of SUN2.https://www.ncbi.nlm.nih.gov/pubmed/28077629