Naslov
Hierarchical and redundant lymphocyte subset control precludes cytomegalovirus replication during latent infection

Autori
Polić, Bojan ; Hengel, Hartmut ; Krmpotić, Astrid ; Trgovchich, Joanne ; Pavić, Ivica ; Lučin, Pero ; Jonjić, Stipan ; Koszinowski, Ulrich H.

Izvornik
The Journal of experimental medicine (0022-1007) 188 (1998), 6; 1047-1054

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
cytomegalovirus; latency; reactivation; T lymphocytes; B cell-deficient mice

Sažetak
Reactivation from latent cytomegalovirus (CMV) infection is often associated with conditions of immunosuppression and can result in fatal disease. Whether the maintenance of systemic CMV latency is mainly governed by factors of the infected cell or by immune control functions is unknown. Likewise, the putative immune control mechanisms which could prevent the induction and spread of recurrent CMV infection are not clearly identified. We took advantage of latently infected B cell-deficient mice and a sensitive method for virus detection to study CMV reactivation after ablation of lymphocyte subsets. A crucial role of both T lymphocytes and NK cells was demonstrated. Within 5 days after depletion of lymphocytes, productive infection occured in 50 % of mice and 14 days later 100 % of mice exhibited recurrent infection. A hierarchy of immune control functions of CD8+, NK and CD4+ cells was established. Reactivation was rare if only one of the lymphocyte subsets was depleted, but evident after removal of a further subset, indicating a functional redundancy of control mechanisms. The salivary glands were identified as the site of most rapid virus shedding, followed by the detection of recurrent virus in the lungs and eventually in the spleen. Our findings document a previously unknown propensity of latent CMV genomes to enter productive infection immediately and with a high frequency after immune cell depletion. The data indicate that only the sustained cellular immune control prevents CMV replication and restricts the viral genome to a systemic state of latency.

Izvorni jezik
Engleski

Znanstvena područja
Veterinarska medicina

POVEZANOST RADA