The Host Range and Interference Properties of Two Closely Related Feline Leukemia Variants Suggest That They Use Distinct Receptors

Abstract

The proviral clones 61E and 61C represent two closely related variants of feline leukemia virus (FeLV) that exhibit significant differences in their biological and pathogenic properties. The major pathogenic determinant has been mapped to the extracellular envelope glycoprotein (Env-SU), but the mechanism by which envelope differences influence pathogenesis is not well understood. Moreover, it is unclear whether these viruses infect the same target cells and/or enter cells using the same receptor. In the present study, we exploited a recently developed single cycle infection assay to examine the host range and interference properties of 61E and 61C FeLVs and found that these two FeLV variants differ significantly in their host ranges and receptor usages. FeLV-61C was found to be an ecotropic virus; the entry of viruses bearing a 61C envelope protein (Env-SU) into cell lines was limited to feline T-cells and feline fibroblasts. In contrast, the host range of 61E includes, in addition to all feline cells examined, some canine, murine, and human cell lines. Feline fibroblast and feline T-cells that expressed 61E envelope were resistant to infection with a virus bearing a 61E Env-SU, whereas these same cells were susceptible to infection by an otherwise similar virus pseudotyped with the 61C Env-SU. This pattern of interference was observed in cells expressing 61E envelope alone, in the absence of other FeLV gene products, demonstrating that interference was mediated specifically by Env-SU. Fibroblast cells chronically infected with a 61C virus were partially resistant to infection with a virus having a 61C Env-SU, but were not resistant to infection by a virus having a 61E Env-SU. On the basis of the current understanding of virus-receptor interactions, the lack of interference between 61E and 61C under conditions where there is significant homologous interference, combined with the differences in their host cell range, leads us to conclude that 61E and 61C use two distinct primary cellular receptors for entry.

Receptors and Entry Cofactors for Retroviruses Include Single and Multiple Transmembrane-Spanning Proteins as well as Newly Described Glycophosphatidylinositol-Anchored and Secreted Proteins

“…Feline leukemia virus (FeLV) is related to MLV, and its members include isolates that have distinct host range properties; these correspond to the four subgroups (A, B, C, and T [122,155,156]). Like MLVs, some FeLVs are restricted to replication in cells from their natural feline host (FeLV-A and FeLV-T) whereas others can replicate in a variety of nonfeline cells (FeLV-B and FeLV-C).…”

“…Cells infected with FeLV-B are in turn targets for FeLV-T replication because FeLV-T requires Pit1 and either FeLV-B SU or FeLIX for entry. It is unclear how frequently FeLV-T variants emerge in the infected cat, because this subgroup of FeLV was only recently identified (122). Because these viruses can infect cells that are already infected with FeLV-B, as well as cells expressing FeLIX, they have a broad range of possible cell targets.…”

Identification of Envelope Determinants of Feline Leukemia Virus Subgroup B That Permit Infection and Gene Transfer to Cells Expressing Human Pit1 or Pit2

“…FeLV was historically categorized into three subgroups (FeLV-A, -B, and -C) on the basis of superinfection interference analyses; a fourth interference group (FeLV-T) was later identified (23,31,32). FeLV-A is the form of FeLV that is transmitted from cat to cat, but the receptor for this virus has not been isolated.…”

Vírus da leucemia felina: análise da classificação da infecção, das técnicas de diagnóstico e da eficácia da vacinação com o emprego de técnicas sensíveis de detecção viral

“…O FeLV é classificado em quatro subgrupos, FeLV-A, B, C e T, identificados geneticamente de acordo com diferenças no gene da SU e, funcionalmente, pela utilização de diferentes receptores para entrada na célula hospedeira (OVERBAUGH & BANGHAM, 2001).…”

“…Essa ampla distribuição é consistente com o fato de que o FeLV-A é encontrado nesses diversos tecidos e células (HOOVER et al, 1977) e pode explicar a vantagem sobre os outros subgrupos no que diz respeito à transmissibilidade. Esse subgrupo pode causar linfomas, mas geralmente promove lesões moderadas na ausência de outros subgrupos (MOSER et al, 1998). O FeLV-B é comumente associado a linfomas (JARRETT et al, 1973;HARTMANN, 2006).…”