HHV Latency Associated Transcript
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. The LAT mainly performs two functions: it suppresses apoptosis so that latently infected host cells stay alive for the reservoir, and suppresses the expression of lytic genes during latent infection. Lytic gene regulation HHV Infected Cell Polypeptide 0 (ICP0) gene is expressed very early during lytic infection, and for this reason is called an immediate-early Herpes gene. In 1991, Farrell and colleagues reported that the 2.0-kb LAT intron terminates at the 5′ end with a 750-base antisense RNA complement for the ICP0 gene. In 2005, Qing-Yin Wang and colleagues from Harvard Medical School concluded, using assays comparing LAT-negative vs. LAT-positive virus strains, that expression of LAT in neurons represses the expression of several lytic gene products, including ICP4 and Thymidine Kinase. LAT expression results in changes to Histones, thus converting portions of viral DNA into a non-productive form known as heterochromatin. Simian varicella virus (SVV) is a Varicellovirus (a Genus of Subfamily Alphaherpesvirinae) which expresses an HHV LAT homolog known as SVV LAT, and an HHV ICP0 analog known as SVV-ORF61 (Open Reading Frame). SVV LAT is encoded such that it contains an antisense copy of SVV-ORF61 and that expression of SVV LAT during latency downregulates expression of ORF61 and other immediate-early SVV gene products. Chromatin insulator LAT DNA contains an activation boundary between activated LAT-DNA and the inactive lytic viral DNA called a chromatin insulator. CCCTC-binding factor (CTCF) is a zinc finger protein which occurs naturally in some human cells. CTCF is localized to the nucleus of cells. CTCF has been shown to naturally