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The multifaceted regulation of transcription in animal and human retroviruses, endogenous retroviruses

Credit: Anaïs BataboudilaEdited by 
Carine Van Lint, University of Brussels ULB, Belgium

Retroviruses are enveloped viruses with a capsid containing two copies of the viral genomic positive sense single-stranded RNA. Retroviruses are responsible for a broad range of diseases in animals and humans, the most common of which is the development of cancers.

Endogenous retroviruses are genomic sequences that originate from ancestral germ line infections by exogenous retroviruses and that have been captured by the host during the course of evolution. Although most endogenous retroviruses are defective and transcriptionally silenced, some are still able to generate retroviral-like particles and proteins.

During infection by exogenous retroviruses, viral particles bind specifically to their target cells, the viral capsid crosses the plasma membrane. The viral RNA genome is retro-transcribed in double-stranded DNA which migrates to the nucleus where it becomes integrated into the cellular genome and packaged into chromatin as all cellular genes are. Retroviruses persist as long as the cell lives providing a mechanism for lifelong infection in the host. The viral long terminal repeats (LTRs), flanking the provirus, allow the synthesis of the viral genomic RNA by the cellular RNA polymerase II. Viral transcription comprises several steps (initiation, pausing, elongation, polyadenylation) and is preceded by multiple events (locus decondensation, nucleosomes remodeling, histones and DNA modifications). In addition to the RNA polymerase II and general transcription factors, negative and positive specific transcription factors are also involved in retroviral silencing and activation.

Infection by retroviruses is characterized by viral latency in infected cells and represents a major barrier to virus eradication. These features are thought to be due to the transcriptional repression of viral expression in vivo, but the molecular mechanisms involved in such repression are not fully elucidated. A better understanding of these mechanisms is critical to identify factors that could be utilized as targets for novel antiviral therapies.

This thematic series published in Retrovirology contain a collection of reviews describing the diversity and heterogeneity of the molecular mechanisms regulating transcription of different retroviruses, thereby revealing the virus-host interactions. 

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Deadline for submissions: 31 June 2023

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