# Double, double toil and trouble: transforming growth factor beta (TGF-β) in HIV infection

## TL;DR

This paper reviews how TGF-β contributes to chronic inflammation and disease progression in HIV, even when the virus is suppressed by treatment.

## Contribution

The paper provides a comprehensive review of TGF-β's paradoxical roles in HIV immunosuppression, fibrosis, and viral latency.

## Key findings

- TGF-β is linked to persistent inflammation and tissue damage in HIV despite antiretroviral therapy.
- TGF-β has complex effects on HIV, including immunosuppression and enhanced viral latency.
- Understanding TGF-β mechanisms may lead to new therapies for HIV persistence.

## Abstract

Despite effective suppression of viral replication by antiretroviral therapy (ART), chronic HIV infection remains characterized by persistent low-level inflammation and progressive tissue damage, contributing to premature aging and an array of comorbidities including cardiovascular disease, HIV-associated neurocognitive disorders, liver disease, and fibrosis of multiple organs. Increased levels of transforming growth factor beta (TGF-β), characteristic of chronic HIV infection even in the context of ART, appear to be a common thread explaining these disparate comorbidities. As a pleiotropic cytokine with both immunosuppressive and pro-fibrotic properties, TGF-β exerts complex and sometimes paradoxical effects on the HIV lifecycle and pathogenesis. This review explores the multifaceted roles of TGF-β in HIV infection, with particular focus on three critical areas: immunosuppression, tissue fibrosis, and the regulation of viral latency. We discuss recent advancements in understanding the often-paradoxical role of TGF-β on HIV replication and latency dynamics, and how its different effects contribute to multiple mechanisms underlying HIV persistence, from inhibited immune responses and enhanced viral latency to impaired immune reconstitution. A more comprehensive understanding of the mechanisms by which TGF-β contributes to HIV persistence may illuminate novel therapeutic strategies targeting TGF-β signaling pathways for improved HIV treatment and progression toward functional cure.