Tissue origins and immune correlates of viral rebound in SIV-infected rhesus macaques after ART discontinuation.

Viral rebound in SIV-infected rhesus macaques after ART discontinuation originates from limited tissue sites, primarily the gastrointestinal tract, involving 1 to 38 lineages per animal.

• Why it matters: Understanding the tissue sources and immune factors driving viral rebound is crucial for developing strategies to achieve sustained ART-free remission in HIV-1-infected individuals.
• What they did: The study analyzed 16 rhesus macaques treated with ART for 70 weeks, using molecular barcoding and tissue sampling to identify rebound lineages and their origins, alongside blood transcriptomic and proteomic profiling.
• The result: Viral rebound begins with oligofocal expansion of few clonal lineages from tissues like the GI tract, with longer rebound times linked to immune and metabolic signatures that suppress proviral activation, informing future reservoir and biomarker research.