VACV A33 Specific Neutra™ Antibody Products

Vaccinia virus (VACV) is a complex DNA virus from the poxvirus family with a large, linear double-stranded DNA genome. Its replication occurs entirely within the host cell's cytoplasm. VACV produces three distinct infectious forms: intracellular mature virions (MV), intracellular enveloped virions (IEV), and extracellular virions (EV), each with unique morphology and antigenicity. The IMV is the most abundant and primary form that spreads within the host. The EV is critical for cell-to-cell spread. A33 is a membrane protein located on the EV surface and also expressed on the host cell membrane, playing a key role in the virus's extracellular dissemination. Its principal function is facilitating EV-mediated spread.

Fig. 1 The formation of VACV EVs.^{1, 3}

A33 Structure, Modifications and Interactions

A33 is a type II transmembrane protein featuring a hypothetical C-type lectin domain. It undergoes post-translational modifications, primarily N- and O-linked glycosylation, in addition to acetylation and phosphorylation, which impact its stability and function. The luminal domain's disulfide bonds are vital for proper folding. A33 interacts with other viral proteins, like A36 and B5, through its cytoplasmic and transmembrane regions, forming a complex essential for EV envelopment and actin tail formation. The cytoplasmic tail mediates interactions with host cell components, notably elements of the actin cytoskeleton, thereby enabling viral motility.

Importance of A33 for Viral Spread

A33 is indispensable for efficient VACV extracellular spread. It contributes to EV envelope formation, facilitating viral escape from infected cells. Crucially, A33 is central to actin tail formation, providing the propulsive force for EV movement. Absent A33, EVs exhibit impaired cell-to-cell spread, resulting in significantly reduced viral plaque sizes and infectivity. Therefore, A33 plays a pivotal role in VACV virulence and pathogenesis because it is required for efficient virus spread.

Anti-VACV A33 Neutralizing Antibodies

A33 serves as a target for neutralizing antibody responses directed against EV. Both monoclonal and polyclonal antibodies targeting A33 display high neutralizing efficacy in vitro and in vivo. These antibodies disrupt A33 interactions with viral and host cell proteins, hindering EV envelope formation, actin tail generation, and EV spread. A33 represents a promising target for antiviral therapies and vaccine development. VACV, which contains A33, is the basis for the smallpox vaccine, and antibodies that recognize A33 can protect against the variola virus (the causative agent of smallpox). Some antibodies have been identified that bind to A33 with high affinity and can protect against ectromelia virus (mousepox) infection. Additionally, A33 targeted antibodies, provide valuable tools for understanding the mechanisms of VACV spread and pathogenesis.

Fig. 2 The capacity of anti-A33 antibodies to protect against VACV infection in vivo.^{2, 3}

Based on extensive expertise in the field of antibody development, Creative Biolabs provides a wide range of high-quality anti-VACV A33 neutralizing antibodies to global clients, accelerating your research progress.

REFERENCES

1. Bidgood, Susanna R., and Jason Mercer. "Cloak and dagger: alternative immune evasion and modulation strategies of poxviruses." Viruses 7.8 (2015): 4800-4825.
2. Matho, Michael H., et al. "Structural and functional characterization of anti-A33 antibodies reveal a potent cross-species orthopoxviruses neutralizer." PLoS pathogens 11.9 (2015): e1005148.
3. Distributed under Open Access license CC BY 4.0, without modification.