Why does viral RNA sometimes persist after recovery from acute infections?

Abstract

DNA viruses often persist in the body of their host, becoming latent and recurring many months or years later. By contrast, most RNA viruses cause acute infections that are cleared from the host as they lack the mechanisms to persist. However, it is becoming clear that viral RNA can persist after clinical recovery and elimination of detectable infectious virus. This persistence can either be asymptomatic or associated with late progressive disease or nonspecific lingering symptoms, such as may be the case following infection with Ebola or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Why does viral RNA sometimes persist after recovery from an acute infection? Where does the RNA come from? And what are the consequences?

Fig 1. Patterns of virus production over time that maintain human viruses within the population.

Representative patterns are shown for RNA viruses often associated with persistent RNA that can cause late complications and occasionally reactivate (red), viruses that establish latency and reactivate (such as herpesviruses) (purple), and viruses not cleared by the immune response that continue to produce infectious virus (such as HIV and HCV) (blue). HCV, hepatitis C virus; HIV, human immunodeficiency virus.

Fig 2. Sites of RNA persistence following infection.

Tissues in which RNA viruses persist after infection include the nervous system, eyes, joints, lymph nodes, heart, respiratory tract, and testes. SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2.

Fig 3. Mechanisms for suppressing production of infectious virions.

Several mechanisms exist whereby the virus and host can suppress the production of infectious virions to facilitate the survival of infected cells and viral RNA persistence. For example, the virus may acquire mutations that decrease virion assembly, induce innate responses, or decrease RNA synthesis, while the host employs antiviral immune responses that facilitate infected cell survival. DVG, defective viral genome; IFN, interferon; IL, interleukin; PTM, posttranslational modification; TGF, transforming growth factor.