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.

病毒与宿主细胞的结合涉及病毒（糖）蛋白（GP）和宿主细胞表面受体（Cr）（蛋白质或唾液酸（SA））之间的特异性相互作用。缔合焓的大小根据 GP/Cr 结合的热容量 (ΔC _p ) 的变化而随温度变化，禽流感病毒 (AIV) 血凝素 (HA) 与 SA 结合的影响很小 (ΔC _p = 0 kJ /mol/K），但对 HIV gp120 与 CD4 受体的结合影响很大（ΔC _p = -5.0 kJ/mol/K）。这里开发的热力学模型预测 ΔC _p值从 0 到 ~−2.0 kJ/mol/K 对结合虫媒病毒的蚊子中肠细胞数量的温度敏感性影响相对较小，而 ΔC _p的中间值 ~− 3.0 kJ/mol/K 在约 20 °C 的温度下产生峰值结合，如西方马脑炎病毒实验观察到的那样。 ΔC _p的负值越大，在低于约 20 °C 的温度下，虫媒病毒的结合就会大大降低。因此，为了促进低温下的传播，虫媒病毒可能受益于HA/SA的ΔC _p ~ 0 kJ/mol/K，并且有趣的是蓝舌病毒与蠓中肠中的SA结合。对于 HIV gp120:CD4，ΔC _p的较大负值会减少 37 °C 下的结合。然而，更重要的是整个病毒在宿主细胞表面固定时的熵（ _{ΔSa_immob} ）的减少。 ΔS _{a_immob}呈现出一种排斥力，在较高温度下，焓驱动的 GP/Cr 相互作用减弱，难以克服。 ΔS _{a_immob}对于较大直径的病毒更不利（不太有利），因此与较小的病毒相比，在较高温度下显示出结合减弱。有人建议，通过较小的负ΔS _{a_immob}选择小尺寸表型用于感染较温暖宿主的病毒，从而解释了在 dsDNA 病毒的情况下，随着宿主温度从 0 °C 升高到 40 °C，病毒粒子体积减小的观察结果。与同样感染温血脊椎动物的虫媒病毒相比，HIV 的直径较大，为 134 nm，因此具有较大的负 ΔS _{a_immob} ，这会减少其在人体温度下的结合。有人提出，HIV 通过附着因子的先前非特异性结合占据了 ΔS _{a_immob}的大部分熵损失，因此增强了随后在 37°C 下的特异性 gp120:CD4 结合。这与 HIV 附着因子不是必需的但会增加感染的观察结果是一致的。抗病毒治疗应侧重于增加病毒颗粒大小，例如通过氧化锌纳米颗粒与单纯疱疹病毒结合，从而使 ΔS _{a_immob}的负值更大，从而降低 37°C 下的结合亲和力。