Postinternalization inhibition of adenovirus gene expression and infectious virus production in human T-cell lines.
Detection of adenovirus DNA in human tonsillar T cells in the absence of active virus replication suggests that T cells may be a site of latency or of attenuated virus replication in persistently infected individuals. The lytic replication cycle of Ad5 in permissive epithelial cells (A549) was compared to the behavior of Ad5 in four human T-cell lines, Jurkat, HuT78, CEM, and KE37. All four T-cell lines expressed the integrin coreceptors for Ad2 and Ad5, but only Jurkat and HuT78 express detectable surface levels of the coxsackie adenovirus receptor (CAR). Jurkat and HuT78 cells supported full lytic replication of Ad5, albeit at a level approximately 10% of that of A549, while CAR-transduced CEM and KE37 cells (CEM-CARhi and KE37-CARhi, respectively) produced no detectable virus following infection. All four T-cell lines bind and internalize fluorescently labeled virus. In A549, Jurkat, and HuT78 cells, viral proteins were detected in 95% of cells. In contrast, only a small subpopulation of CEM-CARhi and KE37-CARhi cells contained detectable viral proteins. Interestingly, Jurkat and HuT78 cells synthesize four to six times more copies of viral DNA per cell than did A549 cells, indicating that these cells produce infectious virions with much lower efficiency than A549. Similarly, CEM-CARhi and KE37-CARhi cells, which produce no detectable infectious virus, synthesize three times more viral genomes per cell than A549. The observed blocks to adenovirus gene expression and replication in all four human T-cell lines may contribute to the maintenance of naturally occurring persistent adenovirus infections in human T cells.
McNees
Adrienne L
AL
Department of Microbiology and Immunology, 3107 Rollins Research Center, Emory University School of Medicine, Atlanta, GA 30322. gooding@microbio.emory.edu
Mahr
Jeff A
JA
Ornelles
David
D
Gooding
Linda R
LR
D000260:Adenoviruses, Human / Q000472:pathogenicity* / Q000502:physiology; D002460:Cell Line; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D015967:Gene Expression Regulation, Viral; D006801:Humans; D016023:Integrins / Q000378:metabolism; D019169:Jurkat Cells; D011991:Receptors, Virus / Q000378:metabolism; D013601:T-Lymphocytes; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D016023:Integrins; D011991:Receptors, Virus; D014764:Viral Proteins