Identification of a Cellular Cofactor Required for Infection by Feline Leukemia Virus

Abstract

Retroviral infection involves continued genetic variation, leading to phenotypic and immunological selection for more fit virus variants in the host. For retroviruses that cause immunodeficiency, pathogenesis is linked to the emergence of T cell-tropic, cytopathic viruses. Here we show that an immunodeficiency-inducing, T cell-tropic feline leukemia virus (FeLV) has evolved such that it cannot infect cells unless both a classic multiple membrane-spanning receptor molecule (Pit1) and a second coreceptor or entry factor are present. This second receptor component, which we call FeLIX, was identified as an endogenously expressed protein that is similar to a portion of the FeLV envelope protein. This cellular protein can function either as a transmembrane protein or as a soluble component to facilitate infection.

Feline Leukemia Virus-associated Myelopathy in Cats

“…16 This concept was illustrated by the recent identification of an accessory cellular protein termed FeLIX, which is expressed and secreted by feline T-cells. 1 FeLIX supports replication of a variant of FeLV subtype A that is Tcell-tropic and results in fatal immunodeficiency. 1 Similarly, use of a cell-restricted receptor results in the development of pure red-cell aplasia in cats with a prorubricyte-tropic FeLV variant broadly classified as FeLV subtype C. 17 This virus results in impairment of the transition of erythroid precursors from the burstforming unit-erythroid (BFU-E) to the colony-forming unit-erythroid (CFU-E).…”

“…1 FeLIX supports replication of a variant of FeLV subtype A that is Tcell-tropic and results in fatal immunodeficiency. 1 Similarly, use of a cell-restricted receptor results in the development of pure red-cell aplasia in cats with a prorubricyte-tropic FeLV variant broadly classified as FeLV subtype C. 17 This virus results in impairment of the transition of erythroid precursors from the burstforming unit-erythroid (BFU-E) to the colony-forming unit-erythroid (CFU-E). 17 The receptor used by this virus encodes an organic anion transporter protein that is speculated to be involved in the accumulation of heme compounds necessary for the synthesis of hemoglobin at the BFU-E to CFU-E transition stage.…”

La capture d’enveloppe par les rétrovirus

“…À l'inverse, une Env endogène peut aussi faciliter une infection virale. Ainsi, une SU tronquée d'Env endogène de FeLV sert de corécepteur cellulaire lors de l'infection par un isolat thymotrope de FeLV [38]. L'abondance de rétrovirus chimères naturels et l'altération du spectre d'hôte qui découle de la capture d'env présagent de l'influence permanente des interactions entre rétro-éléments endogènes et exogènes.…”

Focus Assay on FeLIX-Dependent Feline Leukemia Virus

“…For the infection of FeLV-T, FeLIX, a truncated Env encoded by a defective endogenous FeLV, is required. FeLIX mediates the infection of FeLV-T by binding a phosphate transporter Pit-1 [1]. The schematic view of the FeLIX-dependent (cognate receptor-independent) infection is shown in Fig.…”

“…This variant was reconstructed to be a replication-competent form by the genetic engineering technique and the determinant of the disease was proved to reside in the env gene of the defective mutant [5,17]. Later, the reconstructed virus was named T-lymphotropic FeLV (FeLV-T) because it does not infect feline fibroblast cell lines but infects feline T-lymphoma cell lines, such as 3201 cells [1,9,10].…”