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Retrovirus infection strongly enhances scrapie infectivity release in cell culture.

ABSTRACT: Prion diseases are neurodegenerative disorders associated in most cases with the accumulation in the central nervous system of PrPSc (conformationally altered isoform of cellular prion protein (PrPC); Sc for scrapie), a partially protease-resistant isoform of the PrPC. PrPSc is thought to be the causative agent of transmissible spongiform encephalopathies. The mechanisms involved in the intercellular transfer of PrPSc are still enigmatic. Recently, small cellular vesicles of endosomal origin called exosomes have been proposed to contribute to the spread of prions in cell culture models. Retroviruses such as murine leukemia virus (MuLV) or human immunodeficiency virus type 1 (HIV-1) have been shown to assemble and bud into detergent-resistant microdomains and into intracellular compartments such as late endosomes/multivesicular bodies. Here we report that moloney murine leukemia virus (MoMuLV) infection strongly enhances the release of scrapie infectivity in the supernatant of coinfected cells. Under these conditions, we found that PrPC, PrPSc and scrapie infectivity are recruited by both MuLV virions and exosomes. We propose that retroviruses can be important cofactors involved in the spread of the pathological prion agent.

SUBMITTER: Leblanc P

PROVIDER: S-EPMC1500854 | biostudies-other | 2006 Jun

REPOSITORIES: biostudies-other

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Retrovirus infection strongly enhances scrapie infectivity release in cell culture.

Leblanc Pascal P Alais Sandrine S Porto-Carreiro Isabel I Lehmann Sylvain S Grassi Jacques J Raposo Graça G Darlix Jean Luc JL

The EMBO journal 20060525 12

Prion diseases are neurodegenerative disorders associated in most cases with the accumulation in the central nervous system of PrPSc (conformationally altered isoform of cellular prion protein (PrPC); Sc for scrapie), a partially protease-resistant isoform of the PrPC. PrPSc is thought to be the causative agent of transmissible spongiform encephalopathies. The mechanisms involved in the intercellular transfer of PrPSc are still enigmatic. Recently, small cellular vesicles of endosomal origin cal ...[more]

PMID: 16724107

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Project description:Extracellular vesicles (EVs) are involved in intercellular communication in health and disease and affect processes including immune and antiviral responses. We have previously demonstrated that ultracentrifuged serum is depleted of EVs and, when used in cell culture media, is associated with declines in growth and viability of numerous cultured cell types. Although EVs had been reported to enhance or interfere with HIV-1 infection, depending on the setting, the effects of EVs on HIV-1 production and infectivity of released virions were unknown. In this study, we examined the effects of EV-depleted serum on HIV-1 replication in primary cells and cell lines, including two HIV-1 latency models. Cell culture media were prepared with EV-replete fetal bovine serum (FBS) or serum depleted of EVs via ultracentrifugation or a proprietary method (ThermoFisher/Gibco). T-cell and myeloid-lineage cell lines, including ACH-2 and U1 HIV-1 latency models, and primary cells were grown in 10% FBS-based culture media. Cell counts, viability, and proliferation were assessed throughout. HIV-1 production and infectivity were measured by p24 ELISA and luciferase reporter cell lines, respectively. Flow cytometry, Seahorse assays, and miRNA and mRNA expression arrays were done to assess cellular responses to EV-depleted conditions. Significant increases in HIV-1 production were observed in EV-depleted conditions, along with, in some cases, morphology changes and decreased cell viability. Add-back of pelleted EVs reduced HIV-1 production almost to baseline. Primary cells appeared to be less susceptible to EV depletion. ACH-2 and U1 latency models also produced more HIV-1 under EV-depleted conditions. Virus produced under EV-depleted conditions was more infectious. Changes in cellular metabolism and gene expression were associated with EV-depleted culture. The EV environment of HIV-1 infected cells appears to have a significant effect on virus production and infectivity. In cell lines of HIV-latency, significantly higher concentrations of p24 were observed in those cells cultured in EVD conditions. EV-dependence of cell cultures should be examined carefully prior to examining additional experimental variables. However, we also sound a cautionary note that direct actions of EVs may be accompanied by the effects of other, closely associated factors.

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Retrovirus infection strongly enhances scrapie infectivity release in cell culture.

Publications

Retrovirus infection strongly enhances scrapie infectivity release in cell culture.

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