Functional hierarchy of two L domains in porcine endogenous retrovirus (PERV) that influence release and infectivity

Marcucci, Katherine T.; Martina, Yuri; Harrison, Frank; Wilson, Carolyn A.; Salomon, Daniel R.

doi:10.1016/j.virol.2008.02.017

Cited by 14 publications

(15 citation statements)

References 46 publications

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“…The results of the spreading assay correlate to those for the release of MMuLV, shown above, and emphasize the importance of the Gag PPPY motif, but not the PSAP or YPAL motif, in the replication of MMuLV. Likewise, the PPPY motif was recently identified as the dominant L domain in the release of porcine endogenous retrovirus in a functional hierarchy of L-domain activity (19). Yet our results contrast in part with those of a previous report (27) demonstrating a three-to fivefold reduction in VLP levels of MuMLV Gag-YFP harboring the L1 and/or L2 mutations, which suggested a role for PSAP and YPAL motifs in MMuLV budding.…”

contrasting

confidence: 99%

“…Examples of these dual domains include the PTAP and YPDL motifs in HIV Gag (9,28) and the PSAP and PPPY motifs in Mason-Pfizer monkey virus Gag (11) and porcine endogenous retrovirus Gag (19). Recently, it has been proposed that MMuLV Gag is unique in that it possesses three L domains (27): PPPY (nested in the p12 domain), first identified by Yuan et al (35); PSAP (in the MA domain); and YPAL (at the border between the MA and p12 domains).…”

mentioning

confidence: 99%

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Basal Budding and Replication of the Murine Leukemia Virus Are Independent of the Gag L Domains

Sabo

Laham-Karam

Bacharach

2008

J Virol

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Moloney murine leukemia virus (MMuLV) Gag protein contains three identified late (L) domains, PPPY, YPAL, and PSAP, which are thought to interact with the endosomal sorting machinery to assist budding. We created single and combined L-domain mutants in all permutations and tested the resulting clones for budding and replication. Budding and replication of all viruses with mutated PPPY were greatly reduced; however, the basal replication level was retained, demonstrated by the slow spread of the viruses in culture. Mutations in PSAP or YPAL did not affect budding or spreading, demonstrating that these two motifs are dispensable for efficient MMuLV replication. Furthermore, the basal budding level was maintained following inhibition of endosomal sorting machinery, emphasizing that the basal budding of MMuLV is independent of this machinery.

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contrasting

confidence: 99%

mentioning

confidence: 99%

Basal Budding and Replication of the Murine Leukemia Virus Are Independent of the Gag L Domains

Sabo

Laham-Karam

Bacharach

2008

J Virol

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“…Studies implicating different types of viruses have demonstrated that defects in virus release in vitro give rise to in vivo attenuation (18,30,32,53). For a rapidly lytic virus such as EMCV, it seems likely that impaired release would decrease propagation and hence contribute to its attenuated phenotype.…”

Section: Discussionmentioning

confidence: 99%

Encephalomyocarditis Virus 2A Protein Is Required for Viral Pathogenesis and Inhibition of Apoptosis

Carocci

Cordonnier

Huet

et al. 2011

J Virol

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The encephalomyocarditis virus (EMCV), a Picornaviridae virus, has a wide host spectrum and can cause various diseases. EMCV virulence factors, however, are as yet ill defined. Here, we demonstrate that the EMCV 2A protein is essential for the pathogenesis of EMCV. Infection of mice with the B279/95 strain of EMCV resulted in acute fatal disease, while the clone C9, derived by serial in vitro passage of the B279/95 strain, was avirulent. C9 harbored a large deletion in the gene encoding the 2A protein. This deletion was incorporated into the cDNA of a pathogenic EMCV1.26 strain. The new virus, EMCV1.26⌬2A, was capable of replicating in vitro, albeit more slowly than EMCV1.26. Only mice inoculated with EMCV1.26 triggered death within a few days. Mice infected with EMCV1.26⌬2A did not exhibit clinical signs, and histopathological analyses showed no damage in the central nervous system, unlike EMCV1.26-infected mice. In vitro, EMCV1.26⌬2A presented a defect in viral particle release correlating with prolonged cell viability. Unlike EMCV1.26, which induced cytopathic cell death, EMCV1.26⌬2A induced apoptosis via caspase 3 activation. This strongly suggests that the 2A protein is required for inhibition of apoptosis during EMCV infection. All together, our data indicate that the EMCV 2A protein is important for the virus in counteracting host defenses, since ⌬2A viruses were no longer pathogenic and were unable to inhibit apoptosis in vitro.

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“…Virus production was analyzed using an assay for RT activity, which measures virus particles containing RT, or by titration, measuring infectious viruses (297,298,313). Virus production and morphology were studied by transmission electron microscopy (89,192,300) (Fig. 2) or by scanning electron microscopy (154,299) (Fig.…”

Section: Pervsmentioning

confidence: 99%

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

2012

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SUMMARY Xenotransplantation may be a solution to overcome the shortage of organs for the treatment of patients with organ failure, but it may be associated with the transmission of porcine microorganisms and the development of xenozoonoses. Whereas most microorganisms may be eliminated by pathogen-free breeding of the donor animals, porcine endogenous retroviruses (PERVs) cannot be eliminated, since these are integrated into the genomes of all pigs. Human-tropic PERV-A and -B are present in all pigs and are able to infect human cells. Infection of ecotropic PERV-C is limited to pig cells. PERVs may adapt to host cells by varying the number of LTR-binding transcription factor binding sites. Like all retroviruses, they may induce tumors and/or immunodeficiencies. To date, all experimental, preclinical, and clinical xenotransplantations using pig cells, tissues, and organs have not shown transmission of PERV. Highly sensitive and specific methods have been developed to analyze the PERV status of donor pigs and to monitor recipients for PERV infection. Strategies have been developed to prevent PERV transmission, including selection of PERV-C-negative, low-producer pigs, generation of an effective vaccine, selection of effective antiretrovirals, and generation of animals transgenic for a PERV-specific short hairpin RNA inhibiting PERV expression by RNA interference.

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Functional hierarchy of two L domains in porcine endogenous retrovirus (PERV) that influence release and infectivity

Cited by 14 publications

References 46 publications

Basal Budding and Replication of the Murine Leukemia Virus Are Independent of the Gag L Domains

Basal Budding and Replication of the Murine Leukemia Virus Are Independent of the Gag L Domains

Encephalomyocarditis Virus 2A Protein Is Required for Viral Pathogenesis and Inhibition of Apoptosis

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

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