# A Truncated Isoform of Cyclin T1 Could Contribute to the Non-Permissive HIV-1 Phenotype of U937 Promonocytic Cells

## TL;DR

A shorter version of the protein Cyclin T1 in U937 cells may prevent HIV-1 infection by blocking viral gene activity.

## Contribution

Discovery of a truncated Cyclin T1 isoform that contributes to HIV-1 resistance in U937 Minus cells.

## Key findings

- A 50 kDa truncated Cyclin T1 is present only in non-permissive Minus cells.
- Truncated Cyclin T1 inhibits HIV-1 transcription by acting as a dominant negative.
- IFNγ treatment reduces truncated Cyclin T1 levels, suggesting a regulatory mechanism.

## Abstract

The different susceptibility to HIV-1 infection in U937 cells—permissive (Plus) or nonpermissive (Minus)—is linked to the expression in Minus cells of interferon (IFN)-γ inducible antiviral factors such as tripartite motif-containing protein 22 (TRIM22) and class II transactivator (CIITA). CIITA interacts with Cyclin T1, a key component of the Positive-Transcription Elongation Factor b (P-TEFb) complex needed for the efficient transcription of HIV-1 upon interaction with the viral transactivator Tat. TRIM22 interacts with CIITA, recruiting it into nuclear bodies together with Cyclin T1. A 50 kDa Cyclin T1 was found only in Minus cells, alongside the canonical 80 kDa protein. The expression of this truncated form remained unaffected by proteasome inhibitors but was reduced by IFNγ treatment. Unlike the nuclear full-length protein, truncated Cyclin T1 was also present in the cytoplasm, and this subcellular localization correlated with its capacity to inhibit Tat-mediated HIV-1 transcription. The 50 kDa Cyclin T1 in Minus cells likely contributes to their non-permissive phenotype by acting as a dominant negative factor, disrupting P-TEFb complex formation and function. Its reduction upon IFNγ treatment suggests a regulatory loop by which its inhibitory role on HIV-1 replication is then exerted by the IFNγ-induced CIITA, which binds to the canonical Cyclin T1, displacing it from the P-TEFb complex.