Zika virus entry and attachment factors (ZIKV entry factors)

Zika virus (ZIKV) entry and attachment factors comprise a diverse group of host cell surface molecules that facilitate the initial stages of viral infection. The process typically involves an initial attachment phase mediated by heparan sulfate proteoglycans (HSPGs) or C-type lectins such as DC-SIGN (CD209), followed by a more specific interaction with entry receptors that trigger clathrin-mediated endocytosis. Key entry receptors include members of the TAM (AXL, Tyro3, MERTK) and TIM (TIM-1, TIM-4) families, which normally function in the recognition of phosphatidylserine on apoptotic cells—a mechanism known as apoptotic mimicry. AXL receptor tyrosine kinase is particularly significant in ZIKV research due to its high expression in neural progenitor cells and its role in dampening the innate immune response, although its necessity for infection in vivo remains a subject of debate. Therapeutic strategies targeting these factors include small-molecule kinase inhibitors like bemcentinib (R428), as well as broad-spectrum entry inhibitors like atovaquone and epigallocatechin gallate (EGCG). Challenges in targeting these factors include the high degree of redundancy among entry pathways and the potential for adverse effects due to the receptors' roles in normal immune homeostasis and development.

Other names

Zika virus receptorsZIKV attachment factorsTAM receptors (AXL, Tyro3, MERTK)TIM receptors (TIM-1, TIM-4)AXL receptor tyrosine kinaseDC-SIGN (CD209)T-cell immunoglobulin and mucin domain-containing protein 1 (TIM-1)Heparan sulfate proteoglycans (HSPGs)Integrin alpha-V beta-3

Inhibition of viral attachment to host cell surface factors; blockade of receptor-mediated endocytosis; inhibition of endosomal acidification to prevent viral-host membrane fusion; competitive binding to the viral envelope (E) protein; and inhibition of host kinase signaling (e.g., AXL) that facilitates viral replication by suppressing innate immunity.