Mus cervicolor Murine Leukemia Virus Isolate M813 Belongs to a Unique Receptor Interference Group

Abstract

Murine leukemia virus (MuLV) M813 was originally isolated from the Southeast Asian rodent Mus cervicolor. As with the ecotropic MuLVs derived from Mus musculus, its host range is limited to rodent cells. Earlier studies have mapped its receptor to chromosome 2, but it has not been established whether M813 shares a common receptor with any other MuLVs. In this study, we have performed interference assays with M813 and viruses from four interference groups of MuLV. The infection efficiency of M813 was not compromised in cells expressing any one of the other MuLVs, demonstrating that M813 must use a distinct receptor for cell entry. The entire M813 env coding region was molecularly cloned. Sequence analysis revealed high similarity with other MuLVs but with a unique receptor-binding domain. Substitution of M813 env sequences in Moloney MuLV resulted in a replication-competent virus with a host range and interference profile similar to those of the biological clone M813. M813 thus defines a novel receptor interference group of type C MuLVs.Viral subgroups of the murine C-type viruses have been defined on the basis of host range, generally corresponding to distinct interference groups defined by receptor usage (40). Five distinct interference groups have been established for the well-studied isolates of Mus musculus, and the cellular receptors for these viruses have all been identified (Table 1). Three families of receptors have been characterized for these viruses, all of which share multiple transmembrane-spanning topology and are implicated in transporter activity: (i) cationic amino acid transport for the cationic amino acid transporter (CAT) family (20, 48), (ii) inorganic phosphate transport for the Pit family (18, 37), and (iii) a presumed phosphate transport activity for the newly identified Sgy1 family (44). Whereas some viruses, such as 10A1 murine leukemia virus (10A1 MuLV), recognize several members of the same transporter family (e.g., Pit1 and Pit2) as well as homologous receptors of different species (e.g., mouse, rat, and human) (34), other viruses recognize only one or at most two members of a receptor family and are unable to recognize homologous receptors of other species (e.g., ecotropic MuLV recognizes only the rodent CAT1 and, with less affinity, the CAT3 receptor, but not the CAT2 receptor or CAT homologues of other species) (19, 30). Interestingly, viruses of different interference groups may use the same receptor but show different affinities to homologues in other species (e.g., the xenotropic MuLV does not recognize all murine homologues of its human cellular receptor, all of which, however, are recognized by polytropic MuLVs [5,28,44,50]). Determining the domains in the viral Env protein complex and the receptor molecule which dictate this specificity has been a subject of intense research over the last few years (11).In addition to being isolated from M. musculus, type C retroviruses have also been isolated from Mus caroli (25), Mus cervicolor (7), and, more recently, Mus dunni (9). With ...

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Characterization of Hortulanus Endogenous Murine Leukemia Virus, an Endogenous Provirus That Encodes an Infectious Murine Leukemia Virus of a Novel Subgroup

“…Although HEMV represents a novel subgroup relative to "classical" MLVs, preliminary cross-interference experiments suggest a relationship in receptor usage to M813 (36). A more complete analysis of this relationship will be published separately (C. H. Tipper and J. M. Coffin, unpublished data).…”

“…There is no obvious separation into mouse and nonmouse clades. Finally, HEMV clusters with M813, an exogenous virus that has a rather different host range (36) (Fig. 7C).…”

“…For this reason, we speculated that the loss of information in these regions might render its Env protein nonfunctional. However, during the course of this study, the sequence and partial tropism data of the virus M813 (an exogenous virus of M. cervicolor originally identified by Benveniste et al [4]) were published (36). While not identical, M813 is similar to HEMV in VRA and VRB, raising the possibility that the HEMV env gene might encode a functional product.…”