Abstract
Envelope (env) proteins of certain endogenous retroviruses (ERVs) participate in various pathophysiological processes. In this study, we characterized pathophysiologic properties of two murine leukemia virus-type ERV (MuLV-ERV) env genes cloned from the ovary of C57BL/6J mice. The two env genes (named ENVOV1 and ENVOV2), with 1,926 bp coding region, originated from two MuLV-ERV loci on chromosomes 8 and 18, respectively. ENVOV1 and ENVOV2 were ~75 kDa and predominantly expressed on the cell membrane. They were capable of producing pseudotype murine leukemia virus virions. Tropism trait and infectivity of ENVOV2 were similar to the polytropic env; however, ENVOV1 had very low level of infectivity. Overexpression of ENVOV2, but not ENVOV1, exerted cytotoxic effects and induced expression of COX-2, IL-1β, IL-6, and iNOS. These findings suggest that the ENVOV1 and ENVOV2 are capable of serving as an env protein for virion assembly, and they exert differential cytotoxicity and modulation of inflammatory mediators.
Highlights
Ancient infection of germline cells with exogenous retroviruses established a genome-wide random embedment of proviruses, called endogenous retroviruses (ERVs), and Mendelian genetics governs their inheritance to the offsprings [1]
A subsequent open reading frame analysis revealed that the two full-length murine leukemia virus (MuLV)-ERV env genes, named ENVOV1 and ENVOV2, retain intact coding potential for env glycoproteins of 641 amino acids
While the nucleotide and polypeptide sequences of the ENVOV2 was identical to an env gene of an polytropic murine leukemia virus (MuLV)-related retroviral sequence from NFS/N mice, the ENVOV1 has not been reported yet [31]
Summary
Ancient infection of germline cells with exogenous retroviruses established a genome-wide random embedment of proviruses, called endogenous retroviruses (ERVs), and Mendelian genetics governs their inheritance to the offsprings [1]. Recent studies identified a number of ERVs, which retain intact coding potentials for gag, pol, and/or env genes, and some of them are reported to be associated with a range of normal physiology (e.g., placental morphogenesis) as well as pathogenic processes (e.g., multiple sclerosis, schizophrenia, injury, and chronic fatigue syndrome) [6,7,8,9,10]. The HERV-W env glycoprotein, called syncytin-1, is highly expressed in glial cells within central nervous system of multiple sclerosis, an autoimmune disease, patients [13]. Syncytin-1 and HERV-FRD env glycoprotein, called syncytin-2, are reported to play an essential role during embryonic development by controlling formation of placental syncytiotrophoblasts primarily through their highly
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