Reengineering paramyxovirus tropism.
Receptor specificity is a critical determinant of viral tropism, but the capacity of viruses to switch to alternative receptors has not been extensively studied. Here, we engineered the attachment protein of an attenuated measles virus and generated truly retargeted viruses that are blind to the native receptors CD46 and SLAM, but which propagate efficiently and exclusively via alternative cellular receptors, epidermal growth factor receptor, or CD38. The engineered receptor tropisms were stably maintained during multiple serial virus passage without reversion to native receptor usage, even on cells offering the choice of both native and alternative receptors. We conclude that paramyxoviruses have a remarkably flexible and adaptable entry mechanism.
Hadac
Elizabeth M
EM
Molecular Medicine Program, Mayo Clinic Rochester, Rochester, MN 55905, USA.
Peng
Kah-Whye
KW
Nakamura
Takafumi
T
Russell
Stephen J
SJ
D036541:ADP-ribosyl Cyclase / Q000378:metabolism; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D016466:CHO Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D066246:ErbB Receptors / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism; D008459:Measles virus / Q000235:genetics / Q000502:physiology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism; D011956:Receptors, Cell Surface; D011991:Receptors, Virus / Q000378:metabolism*; D011995:Recombination, Genetic; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D018523:Tropism; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D015703:Antigens, CD; D006023:Glycoproteins; D007136:Immunoglobulins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D014764:Viral Proteins; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D066246:ErbB Receptors; D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1