The herpes simplex virus latency-associated transcript is spliced during the latent phase of infection

Abstract

The herpes simplex virus type 1 latency-associated transcript (LAT) is expressed as a major species 2,100 to 2,200 bases in length and a less abundant one ca. 730 bases shorter in latently infected mouse and rabbit neurons. RNA blot hybridization experiments using 20to 22-base synthetic oligonucleotides and mung bean nuclease protection assays have demonstrated that the smaller LAT species is colinear with the larger one, except for a 730-base intron. On the basis of Northern blot analysis, the spliced species which comprises as much as 50% of the total LAT in latent infections of mice with several strains of herpes simplex virus type 1 and latent infections of rabbits with either the McKrae or the KOS(M) strains of virus is not present in the acute phase of infection. Further and rather surprisingly, in mice latently infected with the KOS(M) strain of virus, the spliced LAT species is considerably less abundant. This suggests that both the strain of virus and the animal in which the latent infection occurs are important in either the processing or stability of spliced LAT. Finally, an exhaustive series of experiments failed to provide convincing evidence that a unique, poly(A)+ species of LAT exists in the latent phase of infection.

Experimental investigation of herpes simplex virus latency

“…Direct demonstration of the ability of HSV to establish and maintain a latent infection in neuronal cells was accomplished by mouse footpad infection, which is followed by latent infection of spinal ganglia (279). This model system is analogous to genital infection of HSV in humans and has been central to describing many of the parameters of latent HSV infection including the identification of the neuron as the site of latent infection, axonal transport of virus through the sciatic nerve, ability of nonreplicating virus to establish latent infections, and characterization of restricted transcription of the latency-specific transcription unit during the latent phase of infection (39,40,60,140,144,173,282,299,300). Furthermore, the model is useful with HSV-2, despite the greater neuropathology of this virus (34).…”

“…This is in keeping with the stability of the neuronal population itself. The number of viral genomes present and the number of neurons expressing the stable intron processed from the LAT do not change with time following establishment of latent infection (136,228,300). In an investigation of any possible role for latency-associated transcription in maintaining viral genomes, Sedarati et al did a very careful quantitative analysis of viral DNA recoverable from 1 to 11 months following the establishment of latent infection in murine dorsal root ganglia by the footpad route of infection.…”

“…Much of our picture of how latent phase transcripts are expressed and how they may function in reactivation is based upon the detailed characterization of these transcripts by Northern blot, S1, and RNase resistance analysis of RNA-DNA and RNA-RNA hybrids (52,57,60,137,178,179,270,271,282,286,299,300,304,305,331,332). For this review, all our mapping data have been correlated with the sequence of the 17syn ϩ strain, and minor differences in sequence between strains noted in the primary references have no impact upon the general picture outlined below.…”

Asian Zika virus isolate significantly changes the transcriptional profile and alternative RNA splicing events in a neuroblastoma cell line

“…To promote replication of the viral genome and evade the host innate immune response, viruses usurp numerous cellular pathways including altering host gene expression [82]. Indeed, viruses that replicate in the nucleus, such as herpes viruses, adenovirus and influenza A virus subvert the cellular RNA splicing machinery to broaden the coding capabilities of the viral genome [83][84][85]. Some viruses also alter splicing of cellular RNAs to promote the virus infectious cycle [82].…”

Identification of the immediate-early products of bovine herpesvirus-1

“…Dele tion of this promoter abolishes synthesis of LAT in neurons (56,156). Most LATs are not polyadenylated (255,256). The closest polyadenylation site is 8.3 to 8.5 kb from the promoter region (56,155).…”