Abstract
The subgroup A through E avian sarcoma and leukosis viruses ASLV(A) through ASLV(E) are a group of highly related alpharetroviruses that have evolved to use very different host protein families as receptors. We have exploited genetic selection strategies to force the replication-competent ASLVs to naturally evolve and acquire mutations to escape the pressure on virus entry and yield a functional replicating virus. In this study, evolutionary pressure was exerted on ASLV(B) virus entry and replication using a secreted for of its Tvb receptor. As expected, mutations in the ASLV(B) surface glycoprotein hypervariable regions were selected that knocked out the ability for the mutant glycoprotein to bind the sTvbS3-IgG inhibitor. However, the subgroup B Rous associated virus 2 (RAV-2) also required additional mutations in the C-terminal end of the SU glycoprotein and multiple regions of TM highlighting the importance of the entire viral envelope glycoprotein trimer structure to mediate the entry process efficiently. These mutations altered the normal two-step ASLV membrane fusion process to enable infection.
Highlights
The subgroup A through E avian sarcoma and leukosis viruses [ASLV(A) through ASLV(E)]are a group of highly related alpharetroviruses that have evolved their env genes encoding the viral envelope glycoproteins from a common ancestor to use members of very different host protein families as receptors to enable efficient virus entry [1,2,3]
RCAS vectors with other envelope glycoprotein subgroups were constructed by replacing the env gene segment containing the RCAS(A)
Glycoprotein and the extracellular region of the TM glycoprotein were nearly identical across the subgroup A-E ASLVs
Summary
Are a group of highly related alpharetroviruses that have evolved their env genes encoding the viral envelope glycoproteins from a common ancestor to use members of very different host protein families as receptors to enable efficient virus entry [1,2,3]. The SU glycoprotein contains the domains important for interaction with a host protein receptor. Through ASLV(E) SU glycoproteins are highly conserved except for five hypervariable domains, vr, vr2, hr, hr2 and vr3 [4,5,6]. A variety of studies have identified hr and hr as the principle binding domains between the viral glycoprotein trimer and the host protein receptor, with vr contributing to the specificity of the receptor interaction for initiating efficient infection [7,8,9,10,11,12]. The TM glycoprotein contains domains responsible for the fusion process of the viral and cellular membranes necessary for Viruses 2019, 11, 500; doi:10.3390/v11060500 www.mdpi.com/journal/viruses
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