Glycoprotein BEdit

Glycoprotein B (gB) is one of the central components of the viral envelope in many herpesviruses. In the prototypical members of the family Herpesviridae such as the Herpes simplex virus type 1 and related species, gB functions as a primary driver of membrane fusion during entry, and it also contributes to cell-to-cell spread and virion assembly. The protein is a major target of the host antibody response and is studied as a candidate antigen in vaccine and therapeutic research. Its behavior exemplifies how a single envelope protein can orchestrate the switch from a stable viral particle to a successful infection unit, a process underpinned by substantial conformational change. The structural and functional properties of gB have been dissected with techniques including Cryo-electron microscopy and X-ray crystallography, placing it in the class III category of viral fusion proteins, a group that includes other well-studied fusion machines and highlights a shared strategy for merging membranes.

Glycoprotein B is a conserved, surface-exposed protein that is broadly represented across alphaherpesviruses. In HSV-1, its gene is part of the viral genome alongside other essential glycoproteins like Glycoprotein D and the Glycoprotein H/Glycoprotein L complex. The protein undergoes maturation in the secretory pathway, acquiring N-linked glycans that influence antigenicity and receptor interactions. The extracellular portion of gB comprises multiple functional domains that participate in receptor engagement, structural rearrangements, and the timing of fusion. These features are preserved across related viruses, enabling researchers to generalize insights about gB’s role in entry and spread beyond a single virus species.

Structure and genetic context

Glycoprotein B is a type I transmembrane glycoprotein with an N-terminal signal sequence that guides its transit through the endoplasmic reticulum and Golgi apparatus. The mature ectodomain contains several conserved domains (commonly described in domain-based schemata as DI–DV) and a cytoplasmic tail that interacts with tegument and other envelope components during virion assembly. The extracellular surface is heavily glycosylated, a feature that shapes immune recognition and helps shield epitopes from some antibody responses. In many studies, antigenic regions within gB—often referred to by antigenic domain designations (e.g., AD-1 through AD-5 in some HSV literature)—are used to map neutralizing epitopes and to guide vaccine design. For readers, see Glycoprotein D and Glycoprotein H/Glycoprotein L for the broader context of entry machinery in Herpes simplex virus and related pathogens.

In HSV-1 and other herpesviruses, gB works in concert with the gH/gL complex and, in many cases, with gD, which binds cellular receptors to initiate the fusion program. The prefusion form of gB is thought to be metastable, transitioning to a postfusion conformation that drives merger of the viral envelope with the host cell membrane. This conformational choreography—a hallmark of class III viral fusion proteins—has been captured in structural studies that reveal how the same molecule rearranges to pull membranes together during fusion. For more on the fusion machinery across viruses, see Class III viral fusion protein.

Role in entry and cell-to-cell spread

Entry of herpesviruses into host cells is a multistep process in which gB’s conformational changes are tightly coordinated with other envelope proteins. Binding of gD to its cellular receptor(s) (such as nectin-1 or HVEM in HSV-1) relieves autoinhibition and promotes activation of the gH/gL complex, which in turn triggers the fusogenic action of gB. The result is fusion of the viral envelope with the host cell membrane, allowing the viral capsid and tegument to enter the cytoplasm. In addition to initiating entry, gB participates in cell-to-cell spread within infected tissues, contributing to viral dissemination and pathology even in the face of immune pressure. Structural and functional studies indicate that gB mediates the actual fusion step, whereas gD and the gH/gL complex regulate the timing and process of fusion.

Researchers use a range of models to study gB function, from purified proteins and pseudotyped particles to intact virions in cell culture. The reliance on gB across diverse cell types helps explain why neutralizing antibodies targeting gB can have broad activity, though real-world protection is complicated by latency, viral diversity, and immune evasion strategies that operate after initial entry. See also Glycoprotein D and Glycoprotein H/Glycoprotein L to understand how the entry apparatus is assembled as a coordinated machine.

Immune recognition and vaccines

Glycoprotein B is a prominent target for the host humoral response. Neutralizing and binding antibodies directed against gB have been described in naturally infected individuals and in vaccine recipients, and these antibodies can block steps in entry or spread in experimental systems. The heavy glycosylation of gB shapes epitope accessibility and contributes to immune evasion, complicating efforts to achieve durable protection with vaccines that focus on a single antigen. Consequently, vaccine strategies have largely explored multicomponent approaches that combine gB with other envelope proteins such as gD or the gH/gL complex, with adjuvants intended to broaden and strengthen T-cell and humoral responses.

Historical vaccine programs against herpesviruses have highlighted the challenges of achieving meaningful protection, particularly in the presence of latent infection and the neuronal reservoirs that drive reactivation. Subunit vaccines built around gB—often in conjunction with adjuvants designed to bias toward robust neutralizing antibody responses—have shown immunogenicity in preclinical models and early-phase trials, but translating this into substantial, long-lasting protection in humans remains an active area of research. The broader vaccine landscape also includes attempts to elicit cellular immunity against multiple viral targets to address latency and reactivation, with mixed results to date. See Glycoprotein D and T-cell-mediated immunity for related immune strategies.

Therapeutic and preventive research continues to explore gB as a target for small-molecule fusion inhibitors and for monoclonal antibody therapies that could complement vaccines or antiviral drugs. Structural insights into the prefusion and postfusion states of gB inform drug design by identifying critical conformational transitions that are necessary for fusion to proceed. See also Neutralizing antibody and Viral entry for context on how antibodies and entry inhibitors intersect with viral life cycles.

Evolution and diversity

Within the herpesvirus family, gB shows conservation of core functional features but also variability in sequence and antigenic structure across species and strains. This balance—conservation of essential fusion machinery with diversification in surface-exposed regions—helps explain cross-species insights while also presenting challenges for universal vaccine coverage. Studies of gB across different viruses illuminate how immune pressure and host range have shaped the architecture of this fusion protein, informing both basic biology and translational approaches. See Herpesviridae and Viral glycoproteins for broader evolutionary context.

Research tools and clinical implications

Glycoprotein B is a focal point in structural biology, immunology, and antiviral research. Researchers frequently use recombinant gB ectodomains, virus-like particles, and pseudoviruses to probe antibody binding, fusion activity, and immune escape. High-resolution structures of gB in different conformations provide templates for understanding the mechanics of fusion and for guiding vaccine and therapeutic design. In clinical contexts, gB-based diagnostics and vaccine platforms are part of ongoing discussions about how best to reduce incidence and severity of mucocutaneous and other herpesvirus–related diseases.