MHVR-independent cell-cell spread of mouse hepatitis virus infection requires neutral pH fusion.
Receptor-specificity is a key determinant of viral tropism. In this report, however, we have demonstrated that cell-associated spread of MHV can bypass the requirement for binding to primary receptors and thereby spread to cells that are resistant to MHV infection. Anti-receptor antibody CC1, which blocks infection by MHV virions, failed to prevent cell-associated spread of MHV to receptor-negative BHK cells or receptor-positive DBT cells. Cell-associated MHV may be utilizing an alternative, low-affinity receptor that is inadequate for functional interaction with MHV virions. Theoretically, dissemination of MHV infection through a receptor-independent, cell-associated mechanism in vivo provides the potential for broader host and tissue range, and for spread of infection despite the presence neutralizing antibodies. Receptor-independent, cell-associated spread of MHV requires neutral pH fusion capability. The low pH-dependent MHV variant OBLV60, which utilizes an endocytic route of entry, does not spread through a receptor-independent mechanism. Additionally, antiviral antibodies that block MHV spike-mediated fusion inhibited cell-associated spread of infection.
Nash
T C
TC
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Gallagher
T M
TM
Buchmeier
M J
MJ
D000818:Animals; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000502:physiology; D015815:Cell Adhesion Molecules; D002459:Cell Fusion; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D006023:Glycoproteins / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000187:drug effects / Q000821:virology; D051379:Mice; D008985:Monensin / Q000494:pharmacology; D006517:Murine hepatitis virus / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology*
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; C087701:Ceacam2 protein, mouse; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D002738:Chloroquine; D008985:Monensin