How virus size and attachment parameters affect the temperature sensitivity of virus binding to host cells:...

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 (ΔC_p) on GP/Cr binding, being little affected for avian influenza virus (AIV) haemagglutinin (HA) binding to SA (ΔC_p = 0 kJ/mol/K) but greatly affected for HIV gp120 binding to CD4 receptor (ΔC_p = -5.0 kJ/mol/K). A thermodynamic model developed here predicts that values of ΔC_p 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 ΔC_p 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 ΔC_p greatly decrease arbovirus binding at temperatures below ~20 °C. Thus to promote transmission at low temperatures, arboviruses may benefit from ΔC_p ~ 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 ΔC_p as for HIV gp120:CD4 diminish binding at 37 °C. Of greater importance, however, is the decrease in entropy of the whole virus (ΔS_{a_immob}) on its immobilisation on the host cell surface. ΔS_{a_immob} presents a repulsive force which the enthalpy-driven GP/Cr interactions weakened at higher temperatures struggle to overcome. ΔS_{a_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 ΔS_{a_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 ΔS_{a_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 ΔS_{a_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 ΔS_{a_immob} more negative, and thus reducing binding affinity at 37 °C.