Introducing point mutations into the ATGs of the putative open reading frames of the HSV-1 gene encoding the latency associated transcript (LAT) reduces its anti-apoptosis activity

Two Small RNAs Encoded within the First 1.5 Kilobases of the Herpes Simplex Virus Type 1 Latency-Associated Transcript Can Inhibit Productive Infection and Cooperate To Inhibit Apoptosis

“…Conversely, plasmids that express only the first 811 bases of LAT have reduced antiapoptosis functions, and furthermore, deletions of LAT have no antiapoptosis activity (28). Single-point mutations within LAT sRNA1 and sRNA2 reduced the ability of these sRNAs to inhibit apoptosis, which is in agreement with a previous study demonstrating that the same mutations in a large LAT fragment impacted its antiapoptosis functions (7). Although the single-point mutations appear to alter the putative secondary structure of these sRNAs (data not shown), it cannot be ruled out that these mutations had other effects.…”

Herpes Simplex Virus Type 1 (HSV-1)-Induced Apoptosis in Human Dendritic Cells as a Result of Downregulation of Cellular FLICE-Inhibitory Protein and Reduced Expression of HSV-1 Antiapoptotic Latency-Associated Transcript Sequences

“…Moreover, LAT has also been demonstrated to inhibit apoptosis in transfected cells (1,11,12,25,33,49). Importantly, apoptosis initiated by caspase-8 can be blocked by LAT products (11,22,33) and cell lines producing high numbers of LAT do not activate the executioner caspase-3 in response to apoptosis stimuli (12,50). Recently, it has been demonstrated that c-FLIP can substitute for LAT function during reactivation of HSV-1 (32).…”

“…For this purpose, total RNA was extracted at 3, 6, 10, and 18 h after HSV-1 infection and subjected to microarray analyses which include detection of LAT. The latter have been shown to block apoptosis initiated by caspase-8 (11,22,33). Strikingly, at 10 and 18 h p.i., specific probes annealing to HSV-1-encoded LAT (LATI, RH6, LATX, LAT3, and LAT5C) (Fig.…”

The Herpes Simplex Virus 1 Latency-Associated Transcript Promotes Functional Exhaustion of Virus-Specific CD8 + T Cells in Latently Infected Trigeminal Ganglia: a Novel Immune Evasion Mechanism

“…The mouse neuroblastoma cell lines C1300 and Neuro2A have been widely used as neuronal tissue culture models to study various aspects of herpes simplex virus. The LAT ϩ DC-LAT6 and LAT Ϫ DC-⌬LAT311 C1300-derived cell lines and the LAT ϩ JWLAT and LAT Ϫ JW-⌬LAT Neuro2A-derived cell lines have been described previously (12,13,37). JWLAT expresses a shorter region of LAT, LAT nucleotides (nt) 1 to 1499, compared to LAT nt 1 to 3225 for DC-LAT6.…”

“…The very low levels of viral Ag detected during latency suggest that the continuous high-level exposure to Ag that is thought to be necessary to produce CD8 T-cell exhaustion may not occur during HSV-1 latency in mouse TG. It was therefore of interest to determine if LAT alone, in the absence of other viral genes, could contribute to the observed CD8 ϩ T-cell exhaustion, so we examined two mouse neuroblastoma cell lines (Neuro2A cells and C1300 cells) that we had previously independently engineered to stably express LAT (12,13,37 …”