Regulation of herpesvirus macromolecular synthesis VII. Inhibition of internal methylation of mRNA late in infection

Evidence for translational regulation of herpes simplex virus type 1 gD expression

“…We observed no significant changes in the sizes of gD mRNAs made at different times during the replicative cycle, as might be expected if gD mRNAs were spliced late but not early, for example. Clearly, comparisons of gD mRNAs made early 4. Map positions of DNA sequences encoding the gC and gD mRNAs and of DNA sequences cloned in plasmids used as probes to detect these mRNAs.…”

Alphaherpesvirus US3 protein-mediated inhibition of the m6A mRNA methyltransferase complex

“…A potential strategy for uncovering mechanisms that regulate the m6A writer complex is to examine virus-induced regulation of m6A levels. Studies from the 1970s showed that m6A levels in viral and host poly(A) RNA were markedly reduced after infection with the alphaherpesvirus herpes simplex virus 1 (HSV-1) ( Bartkoski and Roizman, 1976 , 1978 ). A recent report also showed that infection of cells with HSV-1 reduces m6A levels ( Srinivas et al, 2021 ).…”

“…This effect depended on the viral ICP27 transcription regulator ( Srinivas et al, 2021 ). However, the early studies on the interaction of alphaherpesviruses with m6A showed that the reduction in m6A methylation depends on an early or catalytic late viral protein, while ICP27 is a non-catalytic immediate-early protein ( Bartkoski and Roizman, 1976 , 1978 , Tombácz et al, 2009 ). In addition, it is currently unknown if expression of ICP27 alone, in the absence of virus infection, affects m6A methylation.…”

Polysome-associated proteins in herpes simplex virus-infected cells

“…In herpes simplex virus (HSV)-infected cells, virus-specific RNA has been shown to be controlled both at the level of transcription and at the level of processing (12,24,25,33). The physical makeup of these viral transcripts is similar to that of the host in being both adenylated and methylated (2,3). The available data may be summarized as follows: (i) mRNA for the a class of polypeptides comes from noncontiguous sites on the HSV genome (7,11); (ii) RNA from the cytoplasm and that from the nucleus show differences in genetic complexity throughout the infectious cycle (12,32,33); (iii) while the translational pattern is changing in the cells, transcripts coding for early protein are present late in infection and are apparently functional (1); and (iv) host mRNA which is apparently still being transcribed is not translated and in fact may be selectively degraded (21).…”

“…(i) The mock-infected cells showed A B C D _ ; Roizman) was used in all experiments. Viral stocks were grown and the titers were determined in Vero cells as previously described (3). Polysomes were purified by Mg" precipitation (22,32).…”