Restricted species tropism of maedi–visna virus strain EV-1 is not due to limited receptor distribution

Abstract

The distribution of receptors for maedi-visna virus (MVV) was studied using co-cultivation assays for virus fusion and PCR-based assays to detect the formation of virus-specific reverse transcription products after virus entry. Receptors were present on cell lines from human, monkey, mouse, chicken, quail, hamster and ovine sources. Thus, the distribution of the receptor for MVV is more similar to that of the amphotropic type C retroviruses than to that of other lentiviruses. The receptor was sensitive to proteolysis by papain, but was resistant to trypsin. Chinese hamster ovary (CHO) and lung cells (V79 TOR) did not express functional receptors for MVV. The receptor was mapped to either chromosome 2 or 4 of the mouse using somatic cell hybrids. This allowed several candidates (e.g. MHC-II, CXCR4) that have been proposed for the MVV receptor to be excluded.

Host Range of Small-Ruminant Lentivirus Cytopathic Variants Determined with a Selectable Caprine Arthritis- Encephalitis Virus Pseudotype System

“…Another significant discrepancy between our results and published work is the species distribution of MVV K1514 receptors. Mouse cells have been shown to form syncytia when expressing MVV EV-1 Env or cocultured with cells expressing MVV K1514 (LV1-1 variant) Env (18,43). In addition, MVV EV-1 can enter mouse cells, indicating that mouse cells can express functional MVV receptors (18).…”

“…Mouse cells have been shown to form syncytia when expressing MVV EV-1 Env or cocultured with cells expressing MVV K1514 (LV1-1 variant) Env (18,43). In addition, MVV EV-1 can enter mouse cells, indicating that mouse cells can express functional MVV receptors (18). Furthermore, hamster-mouse somatic cell hybrids have been used to map the location of the gene encoding the MVV EV-1 receptor to mouse chromosome 2 and/or 4 (18).…”

“…In addition, MVV K1514 virions or recombinant envelope glycoproteins can induce fusion of sheep, goat, human, monkey, mouse, and horse cells (1,8,43), indicating that Icelandic MVV can use receptors from a wide range of species for entry and/or cell-to-cell fusion. Similarly, the envelope glycoproteins of the British MVV strain EV-1 induce syncytia, and this strain enters cells from many different species (18), indicating that wide species tropism of MVV is not limited to the Icelandic strains. In contrast, human cells are refractory to infection by CAEV CO, and this restriction occurs at the receptor level (24), indicating a differential species tropism between ovine and caprine lentiviruses.…”

A maedi–visna virus strain K1514 receptor gene is located in sheep chromosome 3p and the syntenic region of human chromosome 2

“…Although productive MVV replication in vivo is restricted to cells of the monocyte\macrophage lineage and dendritic cells, many cell types express MVV receptors in vitro and possibly in vivo (Brodie et al, 1995 ;Gendelman et al, 1985Gendelman et al, , 1986Georgsson et al, 1989 ;Gorrell et al, 1992 ;Ryan et al, 2000). MVV strains can be segregated into two groups according to recognition of receptors from different species : the Icelandic and British MVV strains K1514 and EV1 can enter cells from a wide range of species, including human, but not Chinese hamster (Cricetulus griseus) cells, while entry of North American MVV strains is restricted to cells of ruminant species (Bruett & Clements, 2001 ;Ho$ tzel & Cheevers, 2001 ;Lyall et al, 2000 ;MacIntyre et al, 1972). However, the identity of the MVV receptor(s) is not known.…”

“…This indicates that distantly related lentiviruses can share receptor usage and suggests the possibility that one of the HIV\SIV coreceptors could also function as an MVV receptor. In this regard, a previous report mapped the MVV-EV1 receptor gene to mouse chromosomes (MMU)-2 and\or -4 and, by assuming a one-component receptor, excluded some HIV and SIV coreceptors, such as CXCR2, CXCR4, CCR1, CCR2, CCR4, CCR5, CCR8 and RDC1, as the receptor used by MVV-EV1 to infect mouse cells (Lyall et al, 2000). The MVV-K1514 receptor gene mapped here may represent a one-component receptor, one component of a two-component receptor with the other component expressed by a hamster gene, or two genes in OAR-3p and HSA-2p25 q13, respectively, forming a two-component receptor.…”