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

https://doi.org/10.1016/j.mran.2020.100104Get rights and content

Highlights

  • Mammalian body temperature presents a constraint on virus binding.

  • Negligible changes in heat capacity promote virus transmission at low temperatures in the case of arboviruses.

  • Observed virus volume/host temperature relationship explained through entropy of virus binding.

  • Non-specific attachment of virus overcomes entropy issues in large viruses such as HIV binding at human body temperature

  • Antivirals such as zinc oxide should focus on the entropy of virus binding as a novel approach.

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.

Keywords

Temperature
Virus size
Entropy
Antivirals
Heat capacity

Abbreviations

AIV
avian influenza virus
BBF
brush border fragments from midgut
BTV
bluetongue virus
Cp
heat capacity at constant pressure
ΔCp
change in heat capacity
Cr
host cell receptor
CD4
host cell receptor for HIV
Ctotal
number of host cells which can bind virus in a given volume of host fluid (midgut or blood)
C.VT
number of host cells with bound virus at temperature T
DENV
Dengue virus
EA
activation energy
EBOV
Zaire ebolavirus
EM
electron microscopy
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
ΔGa_virus_T
change in Gibbs free energy on association of virus and host cell at temperature T
GP
viral (glyco)protein on virus surface that binds to Cr
HA
haemagglutinin
ΔHa_receptor_T
change in enthalpy for binding of virus GP to host Cr receptor at a temperature T
HIV
human immunodeficiency virus
HSV-2
herpes simplex virus type 2
ΔHa_virus_T
change in enthalpy for binding of virus to host cell at temperature T
Ka_virus_T
association constant for binding of virus to host cells at temperature T
Kd_receptor_T
dissociation constant for GP from Cr at temperature T
Kd_virus
dissociation constant for virus from host cell
M
molar (moles dm-3)
n
number of GP/Cr contacts made on virus binding to cell
ptransmissionT
probability of successful infection of the arthropod salivary glands after oral exposure at temperature T
pcompleteT
probability given a virion has bound to the surface of a midgut cell that that midgut cell becomes infected and that its progeny viruses go on to infect the salivary gland so completing the arthropod infection process within the life time of the arthropod at temperature T
R
ideal gas constant
ΔSa_receptor_T
change in entropy for binding of virus GP to host Cr receptor
ΔSa_virus_T
change in entropy for binding of virus to host cell at temperature T
ΔSa_immob
change in entropy on immobilization of whole virus to cell surface
ΔSa_non_specific
change in entropy on immobilization of virus to cell surface through non-specific binding
ΔSa_specific
change in entropy on immobilization of virus to cell surface through specific GP/Cr-driven binding
SA
sialic acid
SIV
simian immunodeficiency virus
Vfree
virus not bound to cells
Vtotal
virus challenge dose in volume of host fluid
WEEV
Western equine encephalitis virus
WNV
West Nile virus
ZnOT
zinc oxide tetrapod

Cited by (0)

View Abstract