title: 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.
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Markel
authors.forename: Elena
authors.initials: E
authors.lastname: Lam
authors.forename: Gabriele
authors.initials: G
authors.lastname: Harste
authors.forename: Sebastian
authors.initials: S
authors.lastname: Darr
authors.forename: Mirja
authors.initials: M
authors.lastname: Ramke
authors.forename: Albert
authors.initials: A
authors.lastname: Heim
mesh_terms: D000260:Adenoviruses, Human / Q000302:isolation & purification* / Q000502:physiology*; D036022:Capsid Proteins / Q000096:biosynthesis; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D012367:RNA, Viral / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000821:virology*; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D036022:Capsid Proteins; D004279:DNA, Viral; D012367:RNA, Viral; C018315:hexon capsid protein, Adenovirus
keywords: adenovirus; carrier state infection; latency; viral persistence