Circular RNAs Associated with Human Cytomegalovirus Infection

Human cytomegalovirus (HCMV) can cause life-threatening diseases in immunocompromised individuals. Moreover, HCMV is the leading cause of virus-associated congenital infections. As one of the eight human herpesviruses, HCMV is particularly associated with a range of neurological impairments, including microcephaly, hearing loss, and developmental delays. Given its significant impact on early development, there is strong motivation to explore alternatives and complements to current antiviral therapies to better mitigate HCMV-associated diseases. Like other herpesviruses, HCMV establishes lifelong infections characterized by alternating latent and lytic phases, enabling the virus to evade immune clearance. These transitions are accompanied by substantial changes in viral and host gene expression, which influence cellular pathways and regulatory mechanisms. Circular RNAs (circRNAs) have recently been identified as products of the HCMV transcriptome and have attracted increasing attention due to their potential roles in infection and pathogenesis. This review focuses on elucidating the functions of HCMV-derived circRNAs, their interactions with both viral and host transcriptomes, and the methodologies used for their identification and analysis. Recent advances in this field have expanded our understanding of the HCMV transcriptome and its contribution to disease, highlighting circRNAs as potential candidates for future biomarker or therapeutic studies.