1 research outputs found
Mechanisms of receptor/coreceptor-mediated entry of enveloped viruses
Enveloped viruses enter host cells either through endocytosis, or by direct
fusion of the viral membrane envelope and the membrane of the host cell.
However, some viruses, such as HIV-1, HSV-1, and Epstein-Barr can enter a cell
through either mechanism, with the choice of pathway often a function of the
ambient physical chemical conditions, such as temperature and pH. We develop a
stochastic model that describes the entry process at the level of binding of
viral glycoprotein spikes to cell membrane receptors and coreceptors. In our
model, receptors attach the cell membrane to the viral membrane, while
subsequent binding of coreceptors enables fusion. The model quantifies the
competition between fusion and endocytotic entry pathways. Relative
probabilities for each pathway are computed numerically, as well as
analytically in the high viral spike density limit. We delineate parameter
regimes in which fusion or endocytosis is dominant. These parameters are
related to measurable and potentially controllable quantities such as membrane
bending rigidity and receptor, coreceptor, and viral spike densities.
Experimental implications of our mechanistic hypotheses are proposed and
discussed.Comment: 10 Figure