Cloning of the cellular receptor for amphotropic murine retroviruses reveals homology to that for gibbon ape leukemia virus.

Abstract

The host and tissue specificity of retrovirus infection is largely determined by specific cellular receptors that mediate virus entry. Genes encoding these receptors are widely distributed in the genome, and the receptors identified to date show no sequence similarity. We have identified the cellular receptor for amphotropic murine retroviruses, Ram-i, by screening a rat cDNA expression library introduced into amphotropic virus-resistant hamster cells. The 656-amino acid receptor is homologous to the gibbon ape leukemia virus receptor at both hydrophobic termini but is highly divergent in the central hydrophilic region. Both receptors appear to be integral membrane proteins having multiple membranespanning regions. Identification of this family of receptors will help define the evolutionary relationship between retroviruses and their cellular receptors.Retrovirus infection is initiated by binding of retrovirus envelope proteins to specific cellular receptors. Virus interference and chromosome mapping studies indicate the presence of many receptors that are used by different retroviruses, including at least eight receptors on human cells (1). The four retroviral receptors that have been identified to date show no sequence similarities that might suggest important features of proteins that can serve as retrovirus receptors, and the genes for these receptors are distributed on different chromosomes (2-8). Thus it is important to isolate additional receptors to see whether common features become apparent.Identification of the receptor for amphotropic murine retroviruses is also important because of the wide use of amphotropic retroviral vectors for gene transfer, especially in human gene therapy applications (9). Certain somatic cell types are difficult to infect with amphotropic vectors (e.g., hematopoietic stem cells), and although part of this difficulty may be due to the apparent inability of these vectors to infect nondividing cells, modulation of receptor expression may also play a role.Expression cloning of the amphotropic retrovirus receptor has been difficult due to the ability of the virus to infect many cell types from a wide range of species. Chinese hamster ovary (CHO)

Human PBMC-derived dendritic cells transduced with an adenovirus vector induce cytotoxic T-lymphocyte responses against a vector-encoded antigen in vitro

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