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Permissive XPR1 gammaretrovirus receptors in four mammalian species are functionally distinct in interference tests
Qingping Liu1, Yuhe Yan1, Christine A Kozak1
1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
Abstract:
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.
Insights
Xenotropic/polytropic mouse leukemia viruses (X/P-MLVs) utilize the XPR1 receptor. Distinct XPR1 receptor variations across species influence viral host range and interactions, revealing complex evolutionary adaptations.
Area of Science:
- Virology
- Molecular Biology
- Evolutionary Biology
Background:
- Xenotropic/polytropic mouse leukemia viruses (X/P-MLVs) are gammaretroviruses that depend on the XPR1 receptor for cellular entry.
- The host range of X/P-MLVs is determined by naturally occurring variations in XPR1 receptors and polymorphisms in viral envelope glycoproteins.
Purpose of the Study:
- To investigate the functional distinctions of XPR1 receptors in four mammalian species (Mus dunni, human, rabbit, mink) permissive to X/P-MLVs.
- To elucidate the mechanisms underlying X/P-MLV host tropism and viral-host interactions at the receptor level.
Main Methods:
- Interference assays were employed to assess the functional distinctiveness of XPR1 receptors across different species.
- Sequence comparisons of XPR1 were performed to identify potential receptor-determining regions correlated with observed interference patterns.
Main Results:
- Interference assays revealed functionally distinct XPR1 receptors among the four species studied.
- Distinct interference patterns emerged when cells were pre-infected with different MLV types, suggesting shared but not always fully functional receptor sites.
- XPR1 sequence analysis identified candidate sites in receptor-determining regions that correlated with specific interference patterns.
Conclusions:
- The findings indicate that XPR1 receptor variations significantly shape X/P-MLV host tropism.
- Evolutionary pressures, including adaptation to host receptor polymorphisms and defense mechanisms, likely drove the diversification of X/P-MLV tropism variants.
