Late viral interference induced by transdominant Gag of an endogenous retrovirus

Mura, Manuela; Murcia, Pablo R.; Caporale, Marco; Spencer, Thomas E.; Nagashima, Kunio; Rein, Alan; Palmarini, Massimo

doi:10.1073/pnas.0402877101

Cited by 91 publications

(115 citation statements)

References 25 publications

(21 reference statements)

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…Understanding how these gene transfers influence the immunologic distinction between host "self " and viral "nonself " is of practical importance. Interestingly, several host genes derived from retroviruses limit infection by related viruses (Ikeda and Odaka 1983;Hainaut et al 1990;Mura et al 2004;Aswad and Katzourakis 2012;Fujino et al 2014;Yap et al 2014), demonstrating that lateral gene flow from viruses to their vertebrate hosts can mediate transgenerational immune memory; all known examples are mediated by production of dominant negative proteins. RNA-mediated transgenerational antiviral immunity, while common via the CRISPR/Cas system in prokaryotes (Sorek et al 2008), has thus far been reported in only one metazoan, Caenorhabditis elegans (Rechavi et al 2011).…”

Section: Introductionmentioning

confidence: 99%

piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

Parrish

Fujino

Shiromoto

et al. 2015

RNA

View full text Add to dashboard Cite

Endogenous bornavirus-like nucleoprotein elements (EBLNs) are sequences within vertebrate genomes derived from reverse transcription and integration of ancient bornaviral nucleoprotein mRNA via the host retrotransposon machinery. While species with EBLNs appear relatively resistant to bornaviral disease, the nature of this association is unclear. We hypothesized that EBLNs could give rise to antiviral interfering RNA in the form of PIWI-interacting RNAs (piRNAs), a class of small RNA known to silence transposons but not exogenous viruses. We found that in both rodents and primates, which acquired their EBLNs independently some 25-40 million years ago, EBLNs are present within piRNA-generating regions of the genome far more often than expected by chance alone (P = 8 × 10 −3 -6 × 10 −8 ). Three of the seven human EBLNs fall within annotated piRNA clusters and two marmoset EBLNs give rise to bona fide piRNAs. In both rats and mice, at least two of the five EBLNs give rise to abundant piRNAs in the male gonad. While no EBLNs are syntenic between rodent and primate, some of the piRNA clusters containing EBLNs are; thus we deduce that EBLNs were integrated into existing piRNA clusters. All true piRNAs derived from EBLNs are antisense relative to the proposed ancient bornaviral nucleoprotein mRNA. These observations are consistent with a role for EBLN-derived piRNA-like RNAs in interfering with ancient bornaviral infection. They raise the hypothesis that retrotransposon-dependent virus-to-host gene flow could engender RNA-mediated, sequence-specific antiviral immune memory in metazoans analogous to the CRISPR/Cas system in prokaryotes.

show abstract

Section: Introductionmentioning

confidence: 99%

piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

Parrish

Fujino

Shiromoto

et al. 2015

RNA

View full text Add to dashboard Cite

show abstract

“…Moreover, some newly inserted proviruses acquired a defective Gag polyprotein resulting in a transdominant phenotype able to block late replication steps of related exogenous retroviruses (Mura et al, 2004;Arnaud et al, 2007;Murcia et al, 2007;Armezzani et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Evolutionary dynamics of endogenous Jaagsiekte sheep retroviruses proliferation in the domestic sheep, mouflon and Pyrenean chamois

Sistiaga-Poveda

Jugo

2014

Heredity

View full text Add to dashboard Cite

The oncogenic exogenous Jaagsiekte sheep retrovirus (JSRV), responsible for ovine pulmonary adenocarcinoma, has several endogenous counterparts termed enJSRVs. Although many of these elements have been inactivated over time by the accumulation of deleterious mutations or internal recombination leading to solo long terminal repeat (LTR) formation, several members of enJSRVs have been identified as nearly intact and probably represent recent integration events. To determine the level of enJSRV polymorphism in the sheep population and related species, we have undertaken a study by characterizing enJSRVs copies and independent integration sites in six domestic sheep and two wild species of the sheep lineage. enJSRVs copies were detected by amplifying the env-LTR region by PCR, and for the detection of the insertion sites, we used two approaches: (1) an in silico approach based on the recently published Sheep Reference Genome Assembly (OARv3.0) and (2) an experimental approach based on PCR suppression and inverse PCR techniques. In total, 103 enJSRV sequences were generated across 10 individuals and enJSRV integrations were found on 11 of the 28 sheep chromosomes. These findings suggest that there are still uncharacterized enJSRVs, and that some of the integration sites are variable among the different species, breeds of the same species, subspecies and geographic locations.

show abstract

“…Dominant-negative (DN) mutants of host genes have been proven to be a valuable tool to elucidate viral pathways from entry (9) to exit (34). Naturally selected DN mutants have been shown to contribute to host resistance to retroviruses (10,22), and the artificial expression of a trans-dominant mutant viral gene can render cells resistant to virus infection, a condition termed intracellular immunization (2,37).…”

mentioning

confidence: 99%

Random Screening for Dominant-Negative Mutants of the Cytomegalovirus Nuclear Egress Protein M50

Rupp

Ruzsics

Buser

et al. 2007

J Virol

View full text Add to dashboard Cite

Inactivation of gene products by dominant-negative (DN) mutants is a powerful tool to assign functions to proteins. Here, we present a two-step procedure to establish a random screen for DN alleles, using the essential murine cytomegalovirus gene M50 as an example. First, loss-of-function mutants from a linker-scanning library were tested for inhibition of virus reconstitution with the help of FLP-mediated ectopic insertion of the mutants into the viral genome. Second, DN candidates were confirmed by conditional expression of the inhibitory proteins in the virus context. This allowed the quantification of the inhibitory effect, the identification of the morphogenesis block, and the construction of DN mutants with improved activity. Based on these observations a DN mutant of the homologous gene (UL50) in human cytomegalovirus was predicted and constructed. Our data suggest that a proline-rich sequence motif in the variable region of M50/UL50 represents a new functional site which is essential for nuclear egress of cytomegalovirus capsids.

show abstract

Late viral interference induced by transdominant Gag of an endogenous retrovirus

Cited by 91 publications

References 25 publications

piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

Evolutionary dynamics of endogenous Jaagsiekte sheep retroviruses proliferation in the domestic sheep, mouflon and Pyrenean chamois

Random Screening for Dominant-Negative Mutants of the Cytomegalovirus Nuclear Egress Protein M50

Contact Info

Product

Resources

About