Latency-associated transcript

The latency associated transcript (LAT) is abundantly transcribed in latendy infected neurons (reviewed in Jones, 1998, 2003). Mice, rabbits, or humans latently infected with HSV-1 express LAT. In productively infected cells or latently infected rabbits, an 8.3-Kb transcript is expressed that has the same sense as LAT. Splicing of the 8.3-Kb transcript yields an abundant 2-Kb LAT and an unstable 6.3-Kb LAT. The majority of LAT is not capped, is poly A-, appears to be circular, and is designated as a stable intron. In small animal models, LAT is important but not required for the latency-reactivation cycle (reviewed in Tones, 1998, 2003). The first 1.5 Kb of LAT coding sequences are important for reactivation from latency. It is not clear vriether LAT encodes a protein or is a regulatory RNA. 

Jin L, Pemg G-C, Nesbum AB, Jones C, Wechsler SL (2005) The baculovirus inhibitor of apoptosis gene (cplAP) can restore reactivation of latency to a herpes simplex virus type 1 that does not express the latency associated transcript (LAT). J Virol 79 12286-12295. 

Pemg G-C, Maguen B, Jin L, Mott KR, Osorio N, Slanina SM, Yukht A, Ghiasi H, Nesbum AB, Inman M, Henderson G, Jones C, Wechsler SL (2002) A gene capable of blocking apoptosis can substitute for the herpes simplex virus type 1 latency-associated transcript gene and restore wild-type reactivation levels. J Virol 76 1224-1235. 

In neurons, HSV-1 infection can result in a latent infection. Upon entry, the virion is transported to the nucleus by retrograde transport along the axon. It is currently unknown which viral genes arc involved in the establishment of a latent infection, but de novo viral protein synthesis is not required. However, latency is related to the expression of latency associated transcripts (LAT), which are expressed from a promotor that is highly active in neurons. LATs prevent the lytic replication cycle by down-regulation of genes associated with lytic infection. Reactivation of the latent virus can be induced by different stimuli like stress and UV irradiation. [For more details see (117).]... 

Neipel F, Albrecht J-C, Fleckenstein B (1997) Cell-homologous genes in the Kaposi s sarcoma-associated rhadinovirus human herpesvirus 8 determinants of its pathogenicity. J Virol 71 4187 192 Perng GC, Jones C, Ciacci-Zanella J, Stone M, Henderson G, Yukht A, Slanina SM, Hofman FM, Ghiasi H, Nesburn AB, Wechsler SL (2000) Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science 287 1500-1503 Raftery MJ, Behrens CK, Muller A, Krammer PH, Walczak H, Schonrich G (1999) Herpes simplex virus type 1 infection of activated cytotoxic T cells Induction of fratricide as a mechanism of viral immune evasion. J Exp Med 190 1103 1114... 

Type III latency, characterized by the expression of all EBNAs and LMPs. This transcriptional pattern is characteristic for the acnite phase of infectious mono-nucdeosis but also found to be associated with post transplant lymphoproliferative disorders. 

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