Involvement of Endogenous Retroviruses in Prion Diseases

Abstract

For millions of years, vertebrates have been continuously exposed to infection by retroviruses. Ancient retroviral infection of germline cells resulted in the formation and accumulation of inherited retrovirus sequences in host genomes. These inherited retroviruses are referred to as endogenous retroviruses (ERVs), and recent estimates have revealed that a significant portion of animal genomes is made up of ERVs. Although various host factors have suppressed ERV activation, both positive and negative functions have been reported for some ERVs in normal and abnormal physiological conditions, such as in disease states. Similar to other complex diseases, ERV activation has been observed in prion diseases, and this review will discuss the potential involvement of ERVs in prion diseases.

Differential gene expression in chronic wasting disease‐positive white‐tailed deer (Odocoileus virginianus)

“…All vertebrate genomes studied include integrated RNA viral sequences known as endogenous retroviruses (ERVs), which were previously considered “junk DNA” (Lee, Jeong, Choi, & Kim, ). Several ERV genes, including ERVK13‐1 and ERVK‐24, ERVK‐25, and P11369 (Table ), were identified in this study, suggesting a potential link between CWD and retroviruses.…”

“…Although Pro is not specifically listed in our DEGs, one of the unknown genes may be a form of the protein. Endogenous retroviruses may be activated in prion diseases (Lee et al, ), and previous studies suggest retroviruses can serve as cofactors involved in prion diseases (Leblanc et al, ) potentially altering endocytic pathways (Ashok & Hegde, ). Leblanc et al () suggested retroviruses may increase prion infectivity by acting as transport vectors in the spread of infective prions throughout an individual.…”

“…All vertebrate genomes studied include integrated RNA viral sequences known as endogenous retroviruses (ERVs), which were previously considered "junk DNA" (Lee, Jeong, Choi, & Kim, 2013).…”

Scrapie infection and endogenous retroviral expression in sheep lymphoid tissues

“…Endogenous retroviruses are remnants of past integrations of exogenous retroviruses into the host germline, and form a significant proportion of transposable elements in the genome of most mammalian species (Johnson, 2019). Initially, scrapie infection was shown to activate the expression of endogenous murine leukaemia viruses (MuLV) in the central nervous system of a senescence accelerated mouse strain, SAMP8, and it was suggested that MuLV might accelerate the progression of scrapie pathogenesis (Carp et al, 1999;Lee et al, 2006;Lee et al, 2013). Co-infection of cell lines with scrapie and exogenous retroviruses, such as Moloney MuLV or a small ruminant lentivirus, resulted in enhanced accumulation and/or release of PrP Sc and infectivity from cells (Leblanc et al, 2006;Stanton et al, 2008).…”

“…Scrapie infection of two neuronal cell lines was shown to influence murine ERV expression, and treatment of the cell lines with the anti-prion drug pentosan polysulphate suppressed scrapie-induced MuLV expression (Stengel et al, 2006). Increased expression of class-I endogenous gamma-retroviruses has been observed in the brains of BSE-infected cynomolgus macaques (Greenwood et al, 2011), and elevated levels of specific human ERV families (HERV-L and HERV-W) were found in cerebrospinal fluid of sporadic CJD patients (Jeong et al, 2010;Lee et al, 2013). It is still unclear whether the observed changes of ERV expression during in vitro and in vivo prion infection are a cause or consequence of the infection, but it can be hypothesized that endogenous retroviral elements may contribute to prion disease pathogenesis directly, or indirectly through effects on prion replication.…”