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How virus size and attachment parameters affect the temperature sensitivity of virus binding to host cells: Predictions of a thermodynamic model for arboviruses and HIV

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  • How virus size and attachment parameters affect the temperature sensitivity of virus binding to host cells: Predictions of a thermodynamic model for arboviruses and HIV


    Microb Risk Anal. 2020 Mar 12:100104. doi: 10.1016/j.mran.2020.100104. [Epub ahead of print]
    How virus size and attachment parameters affect the temperature sensitivity of virus binding to host cells: Predictions of a thermodynamic model for arboviruses and HIV.


    Gale P1.

    Author information




    Abstract

    Virus binding to host cells involves specific interactions between viral (glyco)proteins (GP) and host cell surface receptors (Cr) (protein or sialic acid (SA)). The magnitude of the enthalpy of association changes with temperature according to the change in heat capacity (ΔCp) on GP/Cr binding, being little affected for avian influenza virus (AIV) haemagglutinin (HA) binding to SA (ΔCp = 0 kJ/mol/K) but greatly affected for HIV gp120 binding to CD4 receptor (ΔCp = -5.0 kJ/mol/K). A thermodynamic model developed here predicts that values of ΔCp from 0 to ~-2.0 kJ/mol/K have relatively little impact on the temperature sensitivity of the number of mosquito midgut cells with bound arbovirus, while intermediate values of ΔCp of ~-3.0 kJ/mol/K give a peak binding at a temperature of ~20 ?C as observed experimentally for Western equine encephalitis virus. More negative values of ΔCp greatly decrease arbovirus binding at temperatures below ~20 ?C. Thus to promote transmission at low temperatures, arboviruses may benefit from ΔCp ~ 0 kJ/mol/K as for HA/SA and it is interesting that bluetongue virus binds to SA in midge midguts. Large negative values of ΔCp as for HIV gp120:CD4 diminish binding at 37 ?C. Of greater importance, however, is the decrease in entropy of the whole virus (ΔSa_immob) on its immobilisation on the host cell surface. ΔSa_immob presents a repulsive force which the enthalpy-driven GP/Cr interactions weakened at higher temperatures struggle to overcome. ΔSa_immob is more negative (less favourable) for larger diameter viruses which therefore show diminished binding at higher temperatures than smaller viruses. It is proposed that small size phenotype through a less negative ΔSa_immob is selected for viruses infecting warmer hosts thus explaining the observation that virion volume decreases with increasing host temperature from 0 ?C to 40 ?C in the case of dsDNA viruses. Compared to arboviruses which also infect warm-blooded vertebrates, HIV is large at 134 nm diameter and thus would have a large negative ΔSa_immob which would diminish its binding at human body temperature. It is proposed that prior non-specific binding of HIV through attachment factors takes much of the entropy loss for ΔSa_immob so enhancing subsequent specific gp120:CD4 binding at 37 ?C. This is consistent with the observation that HIV attachment factors are not essential but augment infection. Antiviral therapies should focus on increasing virion size, for example through binding of zinc oxide nanoparticles to herpes simplex virus, hence making ΔSa_immob more negative, and thus reducing binding affinity at 37 ?C.
    ? 2020 Elsevier B.V. All rights reserved.



    KEYWORDS:

    AIV, Avian influenza virus; Antivirals; BBF, Brush border fragments from midgut; BTV, Bluetongue virus; C.VT, Number of host cells with bound virus at temperature t; CD4, Host cell receptor for HIV; Cp, Heat capacity at constant pressure; Cr, Host cell receptor; Ctotal, Number of host cells which can bind virus in a given volume of host fluid (midgut or blood); DENV, Dengue virus; EA, Activation energy; EBOV, Zaire ebolavirus; EM, Electron microscopy; Entropy; Env, HIV GP120 trimer envelope protein which binds to a single CD4 molecule; FCT, Fraction of arthropod midgut cells with bound virus at temperature T; GP, Viral (glyco)protein on virus surface that binds to Cr; HA, Haemagglutinin; HIV, Human immunodeficiency virus; Heat capacity; Temperature; Virus size; ΔCp, Change in heat capacity; ΔGA_virus_T, Change in Gibbs free energy on association of virus and host cell at temperature t; ΔHA_receptor_T, Change in enthalpy for binding of virus GP to host Cr receptor at a temperature t


    PMID:32292808PMCID:PMC7110232DOI:10.1016/j.mran.2020.100104
    Free PMC Article

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