Unraveling the Rectal Virome: Microbial Crosstalk, Immune Modulation, and Clinical Outcomes in People with and Vulnerable to HIV

The rectal mucosa houses a large number of viruses with important roles in shaping the local microbial communities and modulating immune responses which could influence host susceptibility to infection and other diseases. Unique composition of the gut microbiome, including the predominance of clinically significant eukaryotic viruses like herpesviruses, CMV, and human papillomavirus, has been described in both people living with HIV (PLWH) and men who have sex with men (MSM) vulnerable to HIV. Despite these insights, the rectal virome and the clinical implications of virome–bacteriome–immune interactions in the rectal mucosa remain poorly understood. In this review, we synthesize existing data on the composition of the rectal virome, its interactions with the bacteriome and the immune system, and implications on clinical outcomes in people living with or vulnerable to HIV. We also highlight the gaps and research needed to further explore and unravel these relationships.