Type dependent patterns of human adenovirus persistence in human T‐lymphocyte cell lines

Abstract

Disseminated adenovirus infections cause significant mortality in stem cell transplanted patients and are suspected to originate from asymptomatic adenovirus persistence ("latency") in lymphocytes. The infection of three human T-lymphocyte lines (Jurkat, PM1, and CEM) with human adenovirus types of species A (HAdV-A31), B (HAdV-B3, -B11), and C (HAdV-C2, -C5) was investigated for 150 days in order to establish in vitro models for adenovirus persistence. HAdV-C5 persisted with continuous production of infectious virus progeny (about 10(7) TCID50 /ml) in PM1 cells. More than 100 copies of HAdV-C5-DNA per cell were detected by real-time PCR but hexon immunostaining showed that only 7.5% of the cells were infected ("carrier state infection"). Coxsackie and adenovirus receptor (CAR) expression was decreased in comparison to mock infected cultures suggesting selection of a semi-permissive subpopulation of PM-1 cells. By contrast, latency of HAdV-DNA (10(-3) -10(-4) copies/cell) without production of infectious virus progeny was observed in HAdV-C2 infection of PM1 and Jurkat, HAdV-A31 infection of PM1, and HAdV-B3 infection of Jurkat cells. In addition, transcription of E1A, DNA polymerase and hexon mRNA was not detected by RT-PCR suggesting an equivalent of clinical "HAdV latency." Persistence of HAdV-DNA was not observed in abortive infections of PM1 cells with HAdV-B3 and -B11 and in productive, lytical infections of Jurkat cells with HAdV-C5, HAdV-B11, and HAdV-A31. In conclusion, lytic and persistent infections with and without production of infectious virus were observed depending on the type of adenovirus. Genetic determinants for viral persistence may be investigated using these newly established infection models.

Persistence and reactivation of human adenoviruses in the gastrointestinal tract

“…Immunohistochemical analysis of viral protein expression suggested a low level of virus production in lymphoid cells which may primarily serve as sites of long-term persistence with leakage of viral particles into the environment. This notion is in line with the carrier state described for other viruses [20] and has recently been demonstrated for HAdV in an in vitro study with T-cell lines [21,22]. In individuals with adequate immune response, small amounts of infectious virus may be eliminated, so permitting limited virus proliferation in epithelial cells and shedding into the stool.…”

Adenovirus infection and disease in paediatric haematopoietic stem cell transplant patients: clues for antiviral pre-emptive treatment

“…However, species C seems not to be associated with higher pathogenicity, as the ratio between species C and the others species remained the same in HAdV digestive infections, systemic infections, and related disease. The higher frequency of species C than of other species detected in paediatric transplant patients reflects their ability to persist frequently in the digestive tract [25,26]. Species A, which is also associated with digestive infections, was the second most frequent species that we found.…”

Persistent development of adomavirus and aquareovirus in a novel cell line from marbled eel with petechial skin haemorrhage

“…Cell lines persistent infection with adenovirus, papillomavirus, polyomavirus, reovirus, birnavirus or nodavirus have been reported (Ahmed, Chakraborty, Graham, Ramig, & Fields, ; Ahmed & Graham, ; Bedell et al, ; Chi et al, ; Delli Bovi, De Simone, Giordano, & Amati, ; Marjara, Thu, & Evensen, ; Markel et al, ; Wen, ). These persistent infections are possibly associated with host cell status and virus type.…”