HHV Latency Associated Transcript (HHV LAT) is a length of RNA which accumulates in cells hosting long-term, or latent, Human Herpes Virus (HHV) infections. The LAT RNA is produced by genetic transcription from a certain region of the viral DNA. LAT regulates the viral genome and interferes with the normal activities of the infected host cell.
Herpes virus may establish lifelong infection during which a reservoir virus population survives in host nerve cells for long periods of time. Such long-term Herpes infection requires a mode of cellular infection known as latent infection. During the latent infection, the metabolism of the host cell is disrupted. While the infected cell would ordinarily undergo an organized death or be removed by the immune system, the consequences of LAT production interfere with these normal processes.
Latency is distinguished from lytic infection; in lytic infection many Herpes virus particles are produced and then burst or lyse the host cell. Lytic infection is sometimes known as "productive" infection. Latent cells harbor the virus for long time periods, then occasionally convert to productive infection which may lead to a recurrence of symptomatic Herpes symptoms.
During latency, most of the Herpes DNA is inactive, with the exception of LAT, which accumulates within infected cells. The region of HHV DNA which encodes LAT is known as LAT-DNA. After splicing, LAT is a 2.0-kilobase transcript (or intron) produced from the 8.3-kb LAT-DNA. The DNA region containing LAT-DNA is known as the Latency Associated Transcript Region.
Apoptosis is the process of normal cell death. In order to maintain a reservoir of latently infected host cells, Herpes virus interferes with apoptosis. HSV-1 LAT expression was once thought to produce interfering micro-RNA (miRNA) which suppress production of Human apoptosis-pathway proteins such as TGF-β1 and SMAD3, but these findings were retracted by the researchers in January 2008. HHV-8 LAT expression similarly produces miRNAs which suppress production of Thrombospondin-1 protein involved in apoptosis and angiogenesis. Expression of LAT also reduces the production of other proteins involved in the apoptosis mechanism, including proteins caspase-8 and caspase-9.
LAT expression regulates the activity of the Herpes genome during latent infection. LAT expression results in the suppression of Herpes lytic genes. Genetic studies of the LAT-DNA have identified a portion known as a chromatin insulator which forms a boundary between activated LAT-DNA and the inactive lytic viral DNA.
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... Further research has shown that HHV-8 LAT produces miRNA which interfere not with expression of TGF-β1 and SMAD3, but reducing the expression of Thrombospondin ...