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Restrictions to HIV-1 replication in resting CD4+T lymphocytes
Ist Teil von
Cell research, 2013-07, Vol.23 (7), p.876-885
Ort / Verlag
England: Nature Publishing Group
Erscheinungsjahr
2013
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
CD4+ T lymphocytes represent the main target cell population of human immunodeficiency virus (HIV). In an activated state, CD4+ T cells residing in lymphoid organs are a major reservoir of ongoing HIV-1 replication in in- fected individuals. In contrast, resting CD4+ T cells are highly resistant to productive HIV-1 infection, yet are mas- sively depleted during disease progression and represent a substantial latent reservoir for the virus in vivo. Barriers preventing replication of HIV-1 in resting CD4+ T cells include a rigid layer of cortical actin and, early after HIV-1 entry, a block that limits reverse transcription of incoming viral RNA genomes. Defining the molecular bases of these restrictions has remained one of the central open questions in HIV research. Recent advances unraveled mechanisms by which HIV-1 bypasses the entry block and established the host cell restriction factor SAMHDI, a deoxynucleoside tripbosphate triphosphohydrolase, as a central determinant of the cellular restriction to HIV-1 reverse transcription in resting CD4+ T cells. This review summarizes our current molecular and pathophysiological understanding of the mnlti-faceted interactions of HIV-1 with resting CD4+ T lymphocytes.