Adenovirus persistence, reactivation, and clinical management

Abstract

Adenoviral infections continue posing a major threat in severely immunocompromised patients including particularly allogeneic stem cell transplant recipients. Although exogenous infections occur in some instances, the majority of invasive events appear to arise from viral reactivation. In the pediatric setting, adenoviruses were demonstrated to persist in the gastrointestinal tract, and the intestinal epithelium serves as the main site of viral replication preceding invasive infection. Regular monitoring of serial stool samples for the presence and load of adenoviruses has therefore become a routine diagnostic tool for post‐transplant patient surveillance, and can serve as a trigger for early initiation of treatment. In the adult setting, the source of infection or reactivation is less clear, and monitoring of peripheral blood specimens is the predominant approach for patient surveillance. Timely initiation of antiviral treatment is reportedly required for prevention or successful control of disseminated disease mediated by adenoviruses, and appropriate diagnostic monitoring is therefore of paramount importance. Currently available antiviral agents and immune therapeutic approaches have not been able to entirely overcome the life‐threatening courses of invasive adenoviral infections in the immunocompromised clinical setting.

High-content image-based drug screen identifies a clinical compound against cell transmission of adenovirus

“…HAdV have a high prevalence 5–8 and are broadly used as gene therapy vectors 9 and oncolytic viruses 10,11 . The high seroprevalence of HAdV-C2/5 12 underlines that HAdV infections are asymptomatic in healthy individuals, but HAdV persist in mucosal lymphocytes, and thereby pose a severe risk for immunosuppressed patients undergoing stem cell transplantation 13 .…”

“…While species A, F and G target the gastrointestinal tract, HAdV-B, C and E cause infections of the respiratory tract, and conjunctivitis is mostly associated with species B and D, but also C types. HAdV-B show the broadest spectrum of tropisms, also infecting the kidney and hematopoietic system 7,13 .…”

<p>Management of Adenoviral Keratoconjunctivitis: Challenges and Solutions</p>

“…17 The stimulation of these adenovirus containing mucosal T-lymphocytes results in reactivation of latent HAdV with consequential leakage of reactivated viruses into intestinal epithelial cells, where adenoviruses undergo replication and subsequent shedding in stool. 11,17,[19][20][21] This is indicative of persistent subclinical HAdV infection of the gut-associated lymphoid tissue. 20 Immunocompetent individuals are likely to shed less HAdV into their stool, in contrast to those who are immunocompromised, where significant amounts of HAdV are released.…”

Adenoviral strategies to overcome innate cellular responses to infection

“…Following acute infection, Ads may establish persistent infections in the host (see review by Thomas Lion [84] in this Issue). The molecular underpinnings of persistent Ad infection are not well characterized, but a recent report demonstrates that Ad may hijack IFN signaling to suppress the lytic cycle and promote persistent infection [85].…”