TRIM34 acts with TRIM5 to restrict HIV and SIV capsids

Abstract

1The HIV-1 capsid protein makes up the core of the virion and plays a critical role in early 2 steps of HIV replication. Due to its exposure in the cytoplasm after entry, HIV capsid is a 3 target for host cell factors that act directly to block infection such as TRIM5 and MxB. 4 Several host proteins also play a role in facilitating infection, including in the protection 5 of HIV-1 capsid from recognition by host cell restriction factors. Through an unbiased 6 screening approach, called HIV-CRISPR, we show that the Cyclophilin A-binding 7 deficient P90A HIV-1 capsid mutant becomes highly-sensitized to TRIM5alpha restriction 8 in IFN-treated cells. Further, the CPSF6-binding deficient, N74D HIV-1 capsid mutant is 9 sensitive to restriction mediated by human TRIM34, a close paralog of the well-10 characterized HIV restriction factor TRIM5. This restriction occurs at the step of reverse 11 transcription, is independent of interferon stimulation and limits HIV-1 infection in key 12 target cells of HIV infection including CD4+ T cells and monocyte-derived dendritic cells. 13 TRIM34 restriction requires TRIM5alpha as knockout or knockdown of TRIM5alpha 14 results in a loss of antiviral activity. TRIM34 can also restrict some SIV capsids. Through 15 immunofluorescence studies, we show that TRIM34 and TRIM5alpha colocalize to 16 cytoplasmic bodies and are more frequently observed to be associated with infecting 17 N74D capsids than with WT capsids. Our results identify TRIM34 as an HIV-1 CA-18 targeting restriction factor and highlight the potential role for heteromultimeric TRIM 19 interactions in contributing restriction of HIV-1 infection in human cells.

CompCorona: A Web Portal for Comparative Analysis of the Host Transcriptome of PBMC and Lung SARS-CoV-2, SARS-CoV, and MERS-CoV

“…It has recently been reported that SARS-CoV-2 can cause acute pulmonary epithelial senescence and subsequent fibrosis, although the exact mechanism is not yet understood (Hong et al, 2022). TRIM34, up-regulated in our study, has been shown to play a role in the restriction of HIV-1 infection and programmed cell death activated by IAV (Ohainle et al, 2019; Wang et al, 2022). HIV-1-induced immune dysfunction has also been linked to early SARS-CoV-2 clearance (Zhao et al, 2020).…”