Viral Surface Spikes: Host Cell Entry, Immune Responses and Evasion, and Implications for Viral Infection, Inhibition and Rebound

The viral surface spike protein is a key determinant in the infection process, allowing virus entry into host cells by binding to cellular receptors and mediating membrane fusion. These spike proteins, often glycoproteins, trigger immune responses (such as cytokine production, B-cell activation, and antigen presentation), making them central to vaccine and therapy efforts. Notable examples of spike glycoproteins include the HIV (and SIV) envelope, SARS-CoV-2 spike, influenza hemagglutinin, RSV fusion, HSV gB, and EBOV GP. These spikes can evade immune surveillance through mechanisms like glycan shields, high sequence mutation rates, antigenic drift, and structural variability, complicating the development of effective vaccines and treatments. Understanding their roles in host cell entry, immune responses, and evasion is essential for developing strategies to inhibit viral entry and address challenges such as antibody or drug resistance and viral rebound.

This research collection will focus on elucidating the multifaceted interactions between viral spikes and host cells, encompassing aspects such as virus entry, immune activation, immune evasion, inhibition strategies, viral resistance and rebound, and host defensive mechanisms. Advances in cutting-edge technologies across virology, immunology, cell biology, and structural biology have greatly accelerated scientific discovery in these fields. By leveraging these technologies, this research topic aims to deepen our understanding of how viruses use surface spikes for adaptation and persistence, shedding light on coevolutionary dynamics between viruses and hosts. This knowledge will ultimately guide the development of more effective vaccines and therapeutics against viral infection and transmissibility.

This research topic, developed in alignment with the objectives of the Duke Center for HIV Structural Biology (DCHSB), has been expanded to include a diverse range of viral pathogens and host systems. We invite submissions of Original Research, Reviews, and Mini-Reviews on the following topics:

• Molecular mechanism of viral spike-mediated host cell entry and immune evasion
• Innate and adaptive immune responses to viral surface spike glycoproteins
• Structure-based vaccine design and antibody therapies targeting viral spike proteins
• Antigenic profiling of spike proteins and strategies to block viral infection and rebound
• Mechanisms of action for anti-spike antibodies, peptide inhibitors, and small molecules
• Spike protein-mediated virus-to-cell fusion and cell-to-cell transmission

Keywords: Viral spike protein, Host cell entry, Immune evasion, Vaccine and therapy, Immune response

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.