Use of different but overlapping determinants in a retrovirus receptor accounts for non-reciprocal interference between xenotropic and polytropic murine leukemia viruses

Neal S Van Hoeven,A Dusty Miller

doi:10.1186/1742-4690-2-76

Abstract

BackgroundRetrovirus infection depends on binding of the retroviral envelope (Env) protein to specific cell-surface protein receptors. Interference, or superinfection resistance, is a frequent consequence of retroviral infection, and occurs when newly-synthesized Env binds to receptor proteins resulting in a block to entry by retroviruses that use the same receptors. Three groups of viruses demonstrate a non-reciprocal pattern of interference (NRI), which requires the existence of both a common receptor utilized by all viruses within the group, and a specific receptor that is used by a subset of viruses. In the case of amphotropic and 10A1 murine leukemia viruses (MLV), the common and specific receptors are the products of two related genes. In the case of avian sarcoma and leukosis virus types B, D, and E, the two receptors are distinct protein products of a single gene. NRI also occurs between xenotropic and polytropic MLV. The common receptor, Xpr1, has been identified, but a specific receptor has yet to be described.ResultsUsing chimeric receptor proteins and interference studies, we have identified a region of Xpr1 that is uniquely utilized by xenotropic MLV and show that this receptor domain is required for non-reciprocal interference.ConclusionWe propose a novel pattern of receptor usage by xenotropic and polytropic MLV to explain the NRI observed between these viruses. We propose that the specific and common receptor determinants for xenotropic and polytropic viruses are simultaneously present in discreet domains of a single Xpr1 protein.

Highlights

Retrovirus infection depends on binding of the retroviral envelope (Env) protein to specific cell-surface protein receptors
Chinese hamster ovary (CHO) cells transduced by retroviral vectors expressing the chimeric receptors AAUU or AAAU were infected with AKR6 or 1E viruses by maintenance of the cells in virus-containing medium or in standard medium for six weeks
Because CHO cells can be infected by some X-murine leukemia viruses (MLV) strains, we used the Env from an X-MLV strain (AKR6) that was unable to mediate transduction of CHO cells even when haXpr1 was overexpressed in the cells (Figure 1, construct AAAA)

Summary

Introduction

Retrovirus infection depends on binding of the retroviral envelope (Env) protein to specific cell-surface protein receptors. Interference, or superinfection resistance, is a frequent consequence of retroviral infection, and occurs when newly-synthesized Env binds to receptor proteins resulting in a block to entry by retroviruses that use the same receptors. In addition to promoting virus entry, the intracellular interaction of a viral Env and its cognate receptor can limit subsequent infection by subsequent viruses that bind the same receptor. This phenotype is referred to as interference or superinfection (page number not for citation purposes).

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