Primary Evidence: Perng GC, Jones C, Ciacci-Zanella J, Stone M, Henderson G, Yukht A, Slanina SM, Hofman FM, Ghiasi H, Nesburn AB, Wechsler SL, Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript, Science 2000 Feb 25;287(5457):1500-3, Medline: 20156773.
Garber DA, Schaffer PA, Knipe DM, A LAT-associated function reduces productive-cycle gene expression during acute infection of murine sensory neurons with herpes simplex virus type 1, J Virol 1997 Aug;71(8):5885-93, Medline: 97366648.
Chen SH, Kramer MF, Schaffer PA, Coen DM, A viral function represses accumulation of transcripts from productive-cycle genes in mouse ganglia latently infected with herpes simplex virus, Virol 1997 Aug;71(8):5878-84, Medline: 97366647.
Thompson RL, Sawtell NM, The herpes simplex virus type 1 latency-associated transcript gene regulates the establishment of latency, J Virol 1997 Jul;71(7):5432-40, Medline: 97332381.
Zabolotny JM, Krummenacher C, Fraser NW, The herpes simplex virus type 1 2.0-kilobase latency-associated transcript is a stable intron which branches at a guanosine, J Virol 1997 Jun;71(6): 4199-208, Medline: 97296222.
Rodahl E, Haarr L, Analysis of the 2-kilobase latency-associated transcript expressed in PC12 cells productively infected with herpes simplex virus type 1: evidence for a stable, nonlinear structure, J Virol 1997 Feb;71(2):1703-7, Medline: 97151168.
Hill JM, Maggioncalda JB, Garza HH Jr, Su YH, Fraser NW, Block TM, In vivo epinephrine reactivation of ocular herpes simplex virus type 1 in the rabbit is correlated to a 370-base-pair region located between the promoter and the 5' end of the 2.0 kilobase latency-associated transcript, J Virol 1996 Oct;70(10):7270-4, Medline: 96386631.
Wu TT, Su YH, Block TM, Taylor JM, Evidence that two latency-associated transcripts of herpes simplex virus type 1 are nonlinear, J Virol 1996 Sep;70(9):5962-7, Medline: 96323112.
Bloom DC, Hill JM, Devi-Rao G, Wagner EK, Feldman LT, Stevens JG, A 348-base-pair region in the latency-associated transcript facilitates herpes simplex virus type 1 reactivation, J Virol 1996 Apr;70(4):2449-59, Medline: 96183892.
Block TM, Deshmane S, Masonis J, Maggioncalda J, Valyi-Nagi T, Fraser NW, An HSV LAT null mutant reactivates slowly from latent infection and makes small plaques on CV-1 monolayers, Virology 1993 Feb;192(2):618-30, Medline: 93134806.
Devi-Rao GB, Goodart SA, Hecht LM, Rochford R, Rice MK, Wagner EK, Relationship between polyadenylated and nonpolyadenylated herpes simplex virus type 1 latency-associated transcripts, J Virol 1991 May;65(5):2179-90, Medline: 91202553.
Farrell MJ, Dobson AT, Feldman LT, Herpes simplex virus latency-associated transcript is a stable intron, Proc Natl Acad Sci U S A 1991 Feb 1;88(3):790-4, Medline: 91126081.
Zwaagstra JC, Ghiasi H, Slanina SM, Nesburn AB, Wheatley SC, Lillycrop K, Wood J, Latchman DS, Patel K, Wechsler SL, Activity of herpes simplex virus type 1 latency-associated transcript (LAT) promoter in neuron-derived cells: evidence for neuron specificity and for a large LAT transcript, J Virol 1990 Oct;64(10):5019-28, Medline: 90376458.
Hill JM, Sedarati F, Javier RT, Wagner EK, Stevens JG, Herpes simplex virus latent phase transcription facilitates in vivo reactivation, Virology 1990 Jan;174(1):117-25, Medline: 90101367.
Sedarati F, Izumi KM, Wagner EK, Stevens JG, Herpes simplex virus type 1 latency-associated transcription plays no role in establishment or maintenance of a latent infection in murine sensory neurons, J Virol 1989 Oct;63(10):4455-8, Medline: 89382797.
Leib DA, Bogard CL, Kosz-Vnenchak M, Hicks KA, Coen DM, Knipe DM, Schaffer PA, A deletion mutant of the latency-associated transcript of herpes simplex virus type 1 reactivates from the latent state with reduced frequency, J Virol 1989 Jul;63(7): 2893-900, Medline: 89259079.
Steiner I, Spivack JG, Lirette RP, Brown SM, MacLean AR, Subak-Sharpe JH, Fraser NW, Herpes simplex virus type 1 latency-associated transcripts are evidently not essential for latent infection, EMBO J 1989 Feb;8(2):505-11, Medline: 89251578.
Krause PR, Croen KD, Straus SE, Ostrove JM, Detection and preliminary characterization of herpes simplex virus type 1 transcripts in latently infected human trigeminal ganglia, J Virol 1988 Dec;62(12):4819-23, Medline: 89037381.
Wagner EK, Flanagan WM, Devi-Rao G, Zhang YF, Hill JM, Anderson KP, Stevens JG, The herpes simplex virus latency-associated transcript is spliced during the latent phase of infection, J Virol 1988 Dec;62(12):4577-85, Medline: 89037343.
Javier RT, Stevens JG, Dissette VB, Wagner EK, A herpes simplex virus transcript abundant in latently infected neurons is dispensable for establishment of the latent state, Virology 1988 Sep;166(1):254-7, Medline: 88322879.
Spivack JG, Fraser NW, Detection of herpes simplex virus type 1 transcripts during latent infection in mice, J Virol 1987 Dec;61(12):3841-7, Medline: 88062935.
Rock DL, Nesburn AB, Ghiasi H, Ong J, Lewis TL, Lokensgard JR, Wechsler SL, Detection of latency-related viral RNAs in trigeminal ganglia of rabbits latently infected with herpes simplex virus type 1, J Virol 1987 Dec;61(12):3820-6, Medline: 88062932.
Stevens JG, Wagner EK, Devi-Rao GB, Cook ML, Feldman LT, RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons, Science 1987 Feb 27;235(4792):1056-9, Medline: 87149014.
Comment: Within this gene are stable introns including a 2 kb transcript at genomic coordinates 119,462 to 121,416. This transcript in turn has an intron from 119,737 to 120,294, and forms a 1.5 kb transcript. The LAT is located in the inverted repeats therefore this gene appears twice in the genome. The folowing annotation is provided by G. Randall.
The major focus of investigations into genes controlling the establishment or maintenance of latency has been the LATs, a family of transcripts, some of which are spliced, spanning the inverted repeats flanking the unique long, UL, sequence.
The full 8.3 kb transcript accumulates at low levels in latently infected neurons while 2.0 kb and 1.5 kb introns processed from the full-length transcript are abundant, Devi-Rao et al.(1991), Krause et al.(1988), Rock et al.(1987), Spivack and Faser (1987), Stevens et al.(1987), Wagner et al.(1988) and Zwaagstra et al.(1990).
These introns are highly stable and appear to be lariat structures, see Farrell et al.(1991), Rodahl and Haarr (1997), Wu et al.(1996) and Zabolotny et al.(1997).
Viruses deleted in LAT have been reported to establish latency at levels within a 3-fold range of the wild type, Bloom et al.(1996), Thompson and Sawtell (1997). Deletion of LATs reduces the capacity of the virus to cause productive infections in mice and reduces the capacity of the virus to replicate following explantation of the neurons, Block et al.(1993), Hill et al.(1990), Javier et al.(1988), Leib et al.(1989), Roizman and Sears (1996), Sedarati et al.(1989) and Steiner et al.(1989). The region of the LAT associated with decreased reactivation has been mapped to a 348 bp sequence in the 5' end, see Bloom et al.(1996) and Hill et al.(1996).
This transcript has not been shown to express open reading frames. Recently Perng et al.(2000) report that sequences encoding the LAT introns can protect neurons from apoptosis and that a virus deleted for LAT induces apoptosis in rabbit trigeminal ganglia at higher levels than the wild-tpe virus. Thus, at least one function of this transcript may be to promote neuronal survival during the maintenance of latent infection.
Chen et al.(1997) and Garber et al.(1997) suggest that viral functions reside within the LAT domain that repress lytic gene expression in vivo. The effectors of these functions are not identified. Irrespective of the final determination of the functions of LATs, the necessary conclusion is that LATs play a role in the maintenance of the latent state rather than in its establishment.