Zika virus (ZIKV) is mainly transmitted via mosquitos, but human-to-human transmissions also occur. The virus is shed into various body fluids including saliva, which represents a possible source of viral transmission. Thus, we here explored whether human saliva affects ZIKV infectivity. We found that physiological concentrations of pooled saliva dose-dependently inhibit ZIKV infection of monkey and human cells by preventing viral attachment to target cells. The anti-ZIKV activity in saliva could not be abrogated by boiling, suggesting the antiviral factor is not a protein. Instead, we found that purified extracellular vesicles (EVs) from saliva inhibit ZIKV infection. Salivary EVs (saEVs) express typical EV markers such as tetraspanins CD9, CD63 and CD81 and prevent ZIKV attachment to and infection of target cells at concentrations that are naturally present in saliva. The anti-ZIKV activity of saliva is conserved but the magnitude of inhibition varies between individual donors. In contrast to ZIKV, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), predominantly spreading via respiratory droplets, is not affected by saliva or saEVs. Our findings provide a plausible explanation for why ZIKV transmission via saliva, i.e. by deep kissing have not been recorded and establish a novel oral innate immune defence mechanism against some viral pathogens.

寨卡病毒（ZIKV）主要通过蚊子传播，但也会发生人与人之间的传播。该病毒会掉入包括唾液在内的各种体液中，唾液代表病毒传播的可能来源。因此，我们在这里探讨了人类唾液是否会影响ZIKV的感染性。我们发现，通过防止病毒附着到靶细胞上，唾液的生理浓度可以剂量依赖性地抑制猴子和人类细胞的ZIKV感染。煮沸不能消除唾液中的抗ZIKV活性，表明抗病毒因子不是蛋白质。相反，我们发现唾液中纯化的细胞外囊泡（EVs）抑制ZIKV感染。唾液EV（saEV）表达典型的EV标记，例如四跨膜CD9，CD63和CD81并以自然存在于唾液中的浓度阻止ZIKV附着和感染靶细胞。唾液的抗ZIKV活性得以保留，但抑制程度因个体供体而异。与ZIKV相比，主要通过呼吸道飞沫传播的严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）不受唾液或saEV的影响。我们的发现为为什么未记录ZIKV通过唾液传播（即通过深吻）的传递提供了合理的解释，并建立了针对某些病毒病原体的新型口服先天免疫防御机制。主要通过呼吸道飞沫传播，不受唾液或saEV的影响。我们的发现为为什么未记录ZIKV通过唾液传播（即通过深吻）的传递提供了合理的解释，并建立了针对某些病毒病原体的新型口服先天免疫防御机制。主要通过呼吸道飞沫传播，不受唾液或saEV的影响。我们的发现为为什么未记录ZIKV通过唾液传播（即通过深吻）的传递提供了合理的解释，并建立了针对某些病毒病原体的新型口服先天免疫防御机制。