Crafty viruses use every trick in the book to evade the forces of their host's immune system. A particularly insidious strategy has now been discovered in use by a virus with which most human beings are infected, herpes simplex virus-1 (HSV-1). This virus spends most of its time hiding in a so-called "latent phase," residing in a select group of neurons. Only occasionally does it flare up into the "productive" phase in which it reproduces, and infects and kills new cells (causing nasty cold sores in the process). Gupta et al. reveal how it is that the virus remains lurking in its latent phase without triggering an immune response that would clear the infection. For the most part, the virus avoids calling attention to itself in the latent phase by not expressing viral proteins that could initiate an immune response. However, it was known to express a gene during this phase called LAT (for latency-associated transcript). Gupta et al. now explain the role of the LAT gene, whose function was unclear because it does not encode a protein. Instead, the authors report, it functions through an encoded microRNA (miRNA). Their experiments show that the miRNA is required to protect infected neuronal cells from apoptosis. The authors then used computational analysis to find candidate target genes and verified that the miR-LAT miRNA caused degradation of mRNAs encoding transforming growth factor-β (TGF-β) and SMAD3 (a protein that functions in TGF-β-induced regulation of gene transcription). TGF-β can inhibit cell proliferation and cause cell death. Thus, the authors propose that HSV-1 helps create its own hiding place by inhibiting apoptotic signaling in the neuronal cells that harbor the latent infection. Sugden discusses the findings in a News and Views piece.
A. Gupta, J. J. Gartner, P. Sethupathy, A. G. Hatzigeorgiou, N. W. Fraser, Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript. Nature 44, 82-85 (2006). [PubMed]
B. Sugden, Virology: Micro mystery solution. Nature 44, 33-34 (2006). [Online Journal]