Editors' ChoiceVirology

Chromatin Structure Contributes to Latency

Science's STKE  30 Jan 2001:
Vol. 2001, Issue 67, pp. tw7
DOI: 10.1126/stke.2001.67.tw7

Understanding viral latency and reactivation is an important aspect of viral biology and may aid development of strategies to control viral infection. Meier developed a clonal NTera2/D1 (NT2) cell line, which is derived from an embryonal teratocarcinoma and which can be induced to differentiate into neurons in culture. These cells were used to study latency and reactivation of human cytomegalovirus, a virus that replicates in neurons. Based on analysis of the viral DNA structure in infected, but latent, cells, Meier showed that at least a portion of the viral genome had reached the nucleus. Viral replication could be stimulated by pretreatment of the cells with retinoic acid to stimulate differentiation, but retinoic acid had no effect if applied after infection. The histone deacetylase inhibitor trichostatin A stimulated expression of viral major immediate early genes, viral replication, and the production of infectious virus undifferentiated NT2 cells. Thus, differences in chromatin structure in differentiated and undifferentiated cells represents one mechanism by which the immediate early gene transcription can be inhibited, thus inhibiting viral replication and promoting latency.

J. L. Meier, Reactivation of the human cytomegalovirus major immediate-early regulatory region and viral replication in embryonal Ntera2 cells: Role of trichostatin A, retinoic acid, and deletion of the 21-base-pair repeats and modulator. J. Virol. 75, 1581-1593 (2001). [Abstract] [Full Text]

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