Students taking my virology course at the University of Leicester get a weekly newsletter containing extra links relevant to the lectures. This week we have been looking at virus genomes and the class notes are from Principles of Molecular Virology, chapter 5.
Ptashne, M. (2004) A genetic switch: phage lambda revisited. Cold Spring Harbor Laboratory.
The first edition of Mark Ptashne’s 1986 book describing the principles of gene regulation in phage lambda became a classic in both content and form, setting a standard of clarity and precise prose that has rarely been bettered. This edition is a reprint of the original text, together with a new chapter updating the story to 2004. Among the striking new developments are recent findings on long-range interactions between proteins bound to widely separated sites on the phage genome, and a detailed description of how gene activation works.
The molecular basis of herpes simplex virus latency. (2012) FEMS microbiology reviews 36(3): 684-705
This review is a double hit – epigenetics and latency! Herpes simplex virus type 1 is a neurotropic herpesvirus that establishes latency within sensory neurones. Following primary infection, the virus replicates productively within mucosal epithelial cells and enters sensory neurones via nerve termini. The virus is then transported to neuronal cell bodies where latency can be established. Periodically, the virus can reactivate to resume its normal lytic cycle gene expression programme and result in the generation of new virus progeny that are transported axonally back to the periphery. The ability to establish lifelong latency within the host and to periodically reactivate to facilitate dissemination is central to the survival strategy of this virus. This review focuses on the mechanisms involved in the regulation of latency that centre on the functions of the virus-encoded latency-associated transcripts (LATs), epigenetic regulation of the latent virus genome and the molecular events that precipitate reactivation.
Epigenetic regulation of HIV-1 transcription. (2011) Epigenomics. 3(4): 487-502
After entry into the target cell and reverse transcription, HIV-1 genes are integrated into the host genome. It is now well established that the viral promoter activity is directly governed by its chromatin environment. Nuc-1, a nucleosome located immediately downstream of the HIV-1 transcriptional initiation site directly impedes long-terminal repeat (LTR) activity. Epigenetic modifications and disruption of Nuc-1 are a prerequisite to the activation of LTR-driven transcription and viral expression. The compaction of chromatin and its permissiveness for transcription are directly dependent on the post-translational modifications of histones such as acetylation, methylation, phosphorylation and ubiquitination. Understanding the molecular mechanisms underlying HIV-1 transcriptional silencing and activation is thus a major challenge in the fight against AIDS and will certainly lead to new therapeutic tools.
Expression strategies of ambisense viruses. (2003) Virus Research 93: 141-150
Among the negative RNA viruses, ambisense RNA viruses occupy a distinct niche. Ambisense viruses contain at least one ambisense RNA segment, i.e. an RNA that is in part of positive and in part of negative polarity. Because of this unique gene organization, one might expect ambisense RNA viruses to borrow expression strategies from both positive and negative RNA viruses. However, they have little in common with positive RNA viruses, but possess many features of negative RNA viruses. Transcription and/or replication of their RNAs appear generally to be coupled to translation. Such coupling might be important to ensure temporal control of gene expression, allowing the two genes of an ambisense RNA segment to be differently regulated. Ambisense viruses can infect one host asymptomatically and in certain cases, they can lethally infect two hosts of a different kingdom.