Permissive XPR1 gammaretrovirus receptors in four mammalian species are functionally distinct in interference tests.

Xenotropic/polytropic mouse leukemia viruses (X/P-MLVs) use the XPR1 gammaretrovirus receptor for entry. X/P-MLV host range is defined by usage of naturally occurring restrictive XPR1 receptors, and is governed by polymorphisms in the virus envelope glycoprotein and in XPR1. Here, we examined receptors of four mammalian species permissive to all X/P-MLVs (Mus dunni, human, rabbit, mink). Interference assays showed the four to be functionally distinct. Preinfection with X-MLVs consistently blocked all nine XPR1-dependent viruses, while preinfection with P-MLVs and wild mouse X/P-MLVs produced distinctive interference patterns in the four cells. These patterns indicate shared usage of independent, but not always fully functional, receptor sites. XPR1 sequence comparisons identified candidate sites in receptor-determining regions that correlate with some interference patterns. The evolutionary record suggests that the X/P-MLV tropism variants evolved to adapt to host receptor polymorphisms, to circumvent blocks by competing viruses or to avoid host-encoded envelope glycoproteins acquired for defense.