# Anelloviruses: From General Biology to Their Role as Biomarkers of Immune Competence in HIV Infection

## TL;DR

Anelloviruses are linked to immune status in HIV patients and could serve as non-invasive biomarkers for monitoring immune health and treatment response.

## Contribution

The paper highlights anelloviruses as novel biomarkers of immune competence in HIV infection.

## Key findings

- Anellovirus levels rise with HIV progression and decline with ART, but do not return to pre-infection levels.
- High Torque teno virus levels correlate with incomplete immune recovery and ART non-response.
- Anelloviruses both activate and disrupt immune pathways, suggesting complex interactions with the immune system.

## Abstract

Viruses of the family Anelloviridae represent a predominant component of the human virome across various anatomical sites, yet their clinical significance remains poorly understood. This review summarizes current data on the dynamics and functional interactions of anelloviruses with the immune system in the context of human immune deficiency virus (HIV) infection. Existing studies indicate that an individual’s complement of anelloviruses (their “anellome”) serves as a highly sensitive indicator of immunocompetence. In the absence of antiretroviral therapy (ART), the viral load and taxonomic diversity of anelloviruses (genera Alphatorquevirus, Betatorquevirus, and Gammatorquevirus) demonstrate a rapid increase, correlating with HIV viral load, a decline in CD4+ T-lymphocyte count, and the CD4/CD8 ratio, reflecting weakened immune surveillance. Upon initiation of antiretroviral therapy (ART), a decrease in anellovirus viral load is observed; however, it likely does not revert to the pre-HIV infection baseline. At the same time, a high baseline level of Torque teno virus (TTV) is associated with incomplete immune recovery and the risk of ART non-response. Anelloviruses exhibit a dual role as both activators of the immune system (via APOBEC3, antibody production, and pro-inflammatory cytokines resulting from Toll-like receptor (TLR) activation) and disruptors of certain signaling pathways (through micro-RNAs and proteins encoded by ORF2). Thus, monitoring the anellome represents a promising non-invasive approach for assessing immune status, risk stratification, and personalizing therapy in patients with HIV infection. Future research should focus on the practical application of anellovirus viral load and diversity as markers of immune status and on clarifying the consequences of the aggregate interaction between HIV modulator proteins and anelloviruses during co-infection.