Immune Evasion by CMV and BK Virus: Lurking Viruses Waiting for the Right Moment to Deliver a Fatal Blow to Individuals With Compromised Immunity.

Human cytomegalovirus (CMV) and BK polyomavirus are archetypal latent DNA viruses that establish lifelong persistence and cause severe disease upon reactivation in immunocompromised hosts. Although they differ markedly in virion architecture, genome size, and coding capacity, both viruses converge on a shared biological principle: durable persistence is achieved through sustained immune invisibility rather than maximal replication. CMV is a large, enveloped double-stranded DNA (dsDNA) virus whose multilayered structure supports the expression of numerous immunomodulatory proteins that disrupt antigen processing and presentation, modulate natural killer cell surveillance, and reshape cytokine and chemokine networks. In contrast, BK virus (BKV) is a small, nonenveloped dsDNA virus that achieves immune evasion through functional minimalism, restricting viral gene expression, limiting antigen availability, and attenuating innate immune sensing pathways. These distinct yet convergent immune evasion strategies complicate diagnosis, constrain the efficacy of antiviral therapies, and promote viral persistence in vulnerable patients. By integrating structural and biological features with mechanisms of immune escape, this review primarily focuses on how immune modulation blurs the classical distinction between latency and active infection, highlighting implications for clinical monitoring, therapy, and emerging immune-guided strategies for the effective control of viral infection in immunocompromised individuals.