Yellow fever virus envelope glycoprotein (E protein)

The Yellow fever virus envelope glycoprotein (commonly referred to as the "E protein") is the principal surface protein of the yellow fever virus (YFV), a member of the Flavivirus genus. It mediates host cell attachment and membrane fusion, essential for viral entry and infection[1][2][5]. The E protein forms homodimers on the virion surface and is organized into three structural domains (I, II, and III), each contributing to its function in cell entry and fusion[1][2]. Domain III contains the primary neutralizing epitopes that interact with host cell receptors and elicit strong immune responses, making the protein the major target of protective neutralizing antibodies in natural infection and vaccination[2][5][9]. Structural rearrangements of E protein are triggered by acidic pH during endosomal entry, leading to trimerization and viral membrane fusion[1][7]. The protein plays a decisive role in viral tropism, virulence, and immunogenicity, and antibodies against it are a key correlate of protective immunity[5][9]. Despite being a validated immune target, no direct-acting antivirals against the E protein are approved clinically; immune responses (vaccines or monoclonal antibodies) provide the main mode of protection[5][9]. The E protein is also used as a diagnostic and vaccine antigen[4].

Other names

Envelope protein (E)YFV E proteinFlavivirus E proteinViral envelope protein

Inhibition of viral attachment to host cell receptors (by antibodies or experimental inhibitors); Blockade of viral membrane fusion (by small molecules or antibodies); Neutralization of viral particles (by binding to critical epitopes on E protein)