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 Topic focuses on exploring the complex interactions between viral spike proteins and host cells. It encompasses a comprehensive analysis of virus entry mechanisms, immune system activation and evasion, and the development of inhibition strategies to combat viral resistance and rebound. 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.

Aligned with the Duke Center for HIV Structural Biology's goals and broadening our scope to include various viral pathogens and host systems, we invite submissions that advance our understanding of these critical viral components. Articles may address, but are not limited to, 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

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Frontiers in Immunology

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