Retroviral Antisense Transcripts and Genes: 33 Years after First Predicted, a Silent Retroviral Revolution? (original) (raw)

Evidence that retroviral transduction is mediated by DNA not by RNA

Proceedings of the National Academy of Sciences, 1990

Retroviral transduction of cellular nucleic acid sequences requires illegitimate RNA or DNA recombination. To test a model that postulates transduction via efficient illegitimate recombination during reverse transcription of viral and cellular RNAs, we have measured the ability of Harvey sarcoma viruses (HaSVs) with artificial 3' termini to recover a retroviral 3' terminus from helper Moloney virus (MoV) by illegitimate and homologous recombination. For this purpose, mouse NIH 3T3 cells were transformed with Harvey proviruses and then superinfected with MoV. The proviruses lacked the 3' long terminal repeat and an untranscribed region of the 5' long terminal repeat to prevent virus regeneration from input provirus. Only 0-11 focus-forming units of HaSV were generated upon MoV superinfection of 3 x 106 cells transformed by Harvey proviruses with MoV-unrelated termini. This low frequency is consistent with illegitimate DNA recombination via random Moloney provirus integration 3' of the transforming viral ras gene in the 10'-kilobase mouse genome. When portions of murine viral envelope (env) genes were attached 3' of ras, 102-105 focus-forming units of HaSV were generated, depending on the extent of homology with env of MoV. These recombinants all contained HaSV-specific sequences 5' and MoV-specific sequences 3' of the common env homology. They were probably generated by recombination during reverse transcription rather than by recombination among either input or secondary proviruses, since (i) the yield of recombinants was reduced by a factor of 10 when the env sequence was flanked by splice signals and (ii) HaSV RNAs without retroviral 3' Abbreviations: HaSV, Harvey sarcoma virus; MoV, Moloney virus; LTR, long terminal repeat; ffu, focus-forming unit(s); pfu, plaqueforming unit(s).

Human retroviral antisense mRNAs are retained in the nuclei of infected cells for viral persistence

Proceedings of the National Academy of Sciences, 2021

Human retroviruses, including human T cell leukemia virus type 1 (HTLV-1) and HIV type 1 (HIV-1), encode an antisense gene in the negative strand of the provirus. Besides coding for proteins, the messenger RNAs (mRNAs) of retroviral antisense genes have also been found to regulate transcription directly. Thus, it has been proposed that retroviruses likely localize their antisense mRNAs to the nucleus in order to regulate nuclear events; however, this opposes the coding function of retroviral antisense mRNAs that requires a cytoplasmic localization for protein translation. Here, we provide direct evidence that retroviral antisense mRNAs are localized predominantly in the nuclei of infected cells. The retroviral 3′ LTR induces inefficient polyadenylation and nuclear retention of antisense mRNA. We further reveal that retroviral antisense RNAs retained in the nucleus associate with chromatin and have transcriptional regulatory function. While HTLV-1 antisense mRNA is recruited to the p...

Translational control of retroviruses

Nature Reviews Microbiology, 2007

Retroviruses are a unique family of RNA viruses that use virally encoded reverse transcriptase (RT) to replicate genomic RNA through a full-length viral DNA intermediate. These viruses have been shown to be present in the genomes of many vertebrates, including fish, rodents, birds, cats, ungulants, non-human primates and humans. Infection by retroviruses causes a wide variety of pathologies, most commonly cancers, such as leukaemias, sarcomas and mammary carcinomas, but retroviral infection can also cause immunodeficiencies, anaemias, arthritis and pneumonia 1. The retroviridae are classified into seven different genera that are named α through to ε retroviruses, as well as the lentiviruses and spumaviruses (see the International Committee on Taxonomy of Viruses database). Historically, retroviruses have been the source of many key discoveries in biology during the twentieth century, including cell transformation, viral and cellular oncogenes, RT and viral transduction, which paved the way to cDNA cloning and design of retroviral vectors for gene therapy 1. This Review will focus on the mechanisms used by retroviruses to ensure the correct viral protein synthesis within the cytoplasm of the host infected cell with particular emphasis on αand γ-retroviruses (whose prototypes are the avian leukosis virus (ALV) and murine leukaemia virus (MLV), respectively) and primate lentiviruses (HIV-1, HIV-2 and simian immunodeficiency virus (SIV)). An overview of the retroviral life cycle. Retroviruses are enveloped RNA viruses that encapsidate two copies of the same capped and polyadenylated (positive sense) RNA molecule that ranges from 8,000 to 11,000

A historical reflection on the discovery of human retroviruses

Retrovirology, 2009

The discovery of HIV-1 as the cause of AIDS was one of the major scientific achievements during the last century. Here the events leading to this discovery are reviewed with particular attention to priority and actual contributions by those involved. Since I would argue that discovering HIV was dependent on the previous discovery of the first human retrovirus HTLV-I, the history of this discovery is also re-examined.

Retrovirus molecular conjugates

Cellular and Molecular Life Sciences (CMLS), 2002

Retrovirus-derived vectors are currently the preferred vectors used for human gene therapy protocols. Serious safety concerns persist, however, which are specifically related to the formation of a replication-competent virus, and no synthesis method currently employed precludes its formation with certainty. For many cell types, a low transduction efficiency results in insufficient

Effects of Retroviruses on Host Genome Function

Annual Review of Genetics, 2008

For millions of years, retroviral infections have challenged vertebrates, occasionally leading to germline integration and inheritance as ERVs, genetic parasites whose remnants today constitute some 7% to 8% of the human genome. Although they have had significant evolutionary side effects, it is useful to view ERVs as fossil representatives of retroviruses extant at the time of their insertion into the germline and not as direct players in the evolutionary process itself. Expression of particular ERVs is associated with several positive physiological functions as well as certain diseases, although their roles in human disease as etiological agents, possible contributing factors, or disease markers—well demonstrated in animal models—remain to be established. Here we discuss ERV contributions to host genome structure and function, including their ability to mediate recombination, and physiological effects on the host transcriptome resulting from their integration, expression, and othe...