A mutant retroviral receptor restricts virus superinfection interference and productive infection.
BACKGROUND
Both cell-free and cell-associated infection routes are important for retroviral dissemination. Regardless of the mechanism, the driving force of retroviral entry is the interaction between the viral envelope and its receptor. To date it remains unclear how decreased affinity of viruses for their receptors affects viral cell-free infection, cell-cell transmission, and spreading kinetics. We have previously characterized a mutant form of the amphotropic murine retrovirus receptor human phosphate transporter 2 (PiT2) wherein the single substitution of a glutamic acid for the lysine residue at position 522 of this receptor is sufficient to render it to function as a gibbon ape leukemia virus (GALV) receptor.


RESULTS
In this study we analyzed the binding affinity of the mutant receptor PiT2K522E and determined that it has a 1000 fold decreased GALV envelope binding affinity compared to the GALV wild type receptor. The decreased affinity does not restrict the initiation of cell-free GALV infection. The diminished binding affinity does, however, correlate with a decrease in the ability of GALV to spread in cells expressing this mutant receptor.


CONCLUSIONS
The reduced ability of GALV to subsequently spread among cells expressing PiT2K522E is likely resulted from reduced cell-cell transmission, the decreased ability of PiT2K522E-expressing cells to establish superinfection interference, and attendant cytopathic affects.
Section on Directed Gene Transfer, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Meihong
M
Liu
Maribeth V
MV
Eiden
D000818:Animals; D016466:CHO Cells; D018920:Coculture Techniques; D006224:Cricetinae; D005822:Genetic Vectors; D015726:Giant Cells / Q000821:virology; D057809:HEK293 Cells; D006790:Host-Parasite Interactions; D006801:Humans; D017989:Leukemia Virus, Gibbon Ape / Q000378:metabolism / Q000472:pathogenicity*; D051379:Mice; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D012192:Retroviridae Infections / Q000821:virology*; D015163:Superinfection / Q000821:virology*; D014762:Viral Interference; D053585:Virus Attachment; D053586:Virus Internalization; D014779:Virus Replication
D011991:Receptors, Virus; C067981:leukemia virus receptor, gibbon ape