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A defining feature of Human T-cell leukaemia virus type 1 (HTLV-1) infection is the establishment of reversible latency that can persist for many years. This latency enables the expansion of infected CD4+ T cells, ultimately contributing to adult T-cell leukaemia (ATL) and inflammatory disease. Sugata et al. identify a viral negative regulatory element within the HTLV-1 proviral genome that governs transcriptional latency. This intragenic silencing element contains binding sites for the master haematopoietic transcription factor, RUNX1. RUNX1 complex binding represses viral expression, thereby reducing viral production, antigen presentation, and susceptibility to cytotoxic T lymphocyte responses. The intragenic silencing element described in their study is unique to HTLV-1 and represents a novel strategy by which the virus achieves lifelong persistence in the host.
How influenza virus non-structural protein NS1 inhibits the activity of nuclear speckles, these liquid-liquid phase separation complexes that control the transcription and post-transcriptional regulation of cellular genes.
Rheumatic symptoms such as joint inflammation and pain are known features of SARS-CoV-2 infection, though the mechanisms remain unclear. Au and colleagues identified the interaction between the viral spike protein and the endothelin-1 (ET-1) signaling pathway as a cause of osteochondral damage. Their study showed that macitentan, an FDA-approved ET-1 receptor antagonist, reduced joint damage and inflammation in a hamster model, suggesting ET-1 as a potential therapeutic target for viral-induced osteoarthritis (OA).
Acute viral infections are typically cleared by the host’s immune system, but certain RNA viruses can establish ‘within host’ persistent infections, for example in the central nervous system (CNS). Neurons within the CNS are a potential site for viral persistence due to the limited capacity of the host to deploy cytolytic and inflammatory defenses in this environment. Subacute sclerosing panencephalitis (SSPE) is a rare but fatal disease caused by persistent infection with measles virus (MeV), often occurring years after acute measles. Despite the availability of effective vaccines, SSPE remains a concern due to vaccine hesitancy and disruptions in vaccination programs.
