Zika Virus Hijacks Extracellular Vesicle Tetraspanin Pathways for Cell-to-Cell Transmission

Abstract

Zika virus is a reemerging infectious disease that spread rapidly across the Caribbean and South America. Infection of pregnant women during the first trimester has been linked to microcephaly, a neurological condition where babies are born with smaller heads due to abnormal brain development.

Tetraspanins: Host Factors in Viral Infections

“…This highlights the tissue tropism of ZIKV infections toward neural tissues but also the ability of the virus to cross both the placental barrier and the blood–brain barrier (BBB) [ 100 ]. Although this ability to traverse the respective barriers remains largely unknown, recent cell culture models provide evidence to suggest that extracellular vesicles (EVs) containing tetraspanins may provide a platform for transport [ 100 , 101 , 102 ]. However, studies in animal models are yet to be undertaken.…”

“…This suggests that EVs not only provide an alternate method for ZIKV infection, but infectious EVs are also capable of evading adaptive immune responses that depend on the recognition of the ZIKV E protein to function. Additionally, ZIKV infection in Vero E6 cells enhanced the production of EVs with sizes and densities that vary from EVs released from uninfected cells [ 101 ]. Since tetraspanins (CD9, CD63, and CD81) were shown to be critical in endosomal sorting complex required for transport (ESCRT)-dependent and -independent EV biogenesis, enhanced EV biogenesis was observed with a concomitant rise in CD63 levels 48 h post ZIKV infection in SNB-19 cells (human glioblastoma cells) [ 101 ].…”

Ticks: More Than Just a Pathogen Delivery Service

“…Interestingly, salivary extracellular vesicles can modulate the outcome of vector-borne infections, as is the case for A. phagocytophilum and Francisella tularensis . Extracellular vesicles also facilitate vector-borne virus infection and transmission (Silvas et al, 2016;Vora et al, 2018;Zhou et al, 2018;Reyes-Ruiz et al, 2019;York et al, 2021). For instance, the Haemaphysalis longicornis-borne virus SFTS (Severe Fever with Thrombocytopenia Syndrome) exploits host-derived vesicles to invade uninfected cells and evade antibody defenses (Silvas et al, 2016).…”

“…For instance, the Haemaphysalis longicornis-borne virus SFTS (Severe Fever with Thrombocytopenia Syndrome) exploits host-derived vesicles to invade uninfected cells and evade antibody defenses (Silvas et al, 2016). Extracellular vesicle cargo can be altered by intracellular vector-borne pathogens, not only by adding pathogen-derived contents but also by changing the composition of host-derived molecules within the vesicles (Regev-Rudzki et al, 2013;Silvas et al, 2016;Vora et al, 2018;Jiang et al, 2020;York et al, 2021). The malaria-causing parasite Plasmodium falciparum commandeers red blood cells exosomes to communicate and exchange genetic material with other parasites during infection (Regev-Rudzki et al, 2013).…”

Are the Organoid Models an Invaluable Contribution to ZIKA Virus Research?

“…As EVs have been shown to cross blood-brain and placental barriers, it is possible that Zika virus could gain access to the brain or developing fetus via this mechanism. In particular, Zika virus-infected cells secrete distinct EV subpopulations with specific viral protein profiles and infectious genomes with respect to those released from non-infected cells [20].…”