ANDV Glycoprotein

ANDV Glycoprotein Full Name

Andes orthohantavirus glycoprotein

ANDV Glycoprotein Introduction

The Andes virus (ANDV) glycoprotein complex consists of two envelope glycoproteins, Gn and Gc, which are encoded by the M segment of the trisegmented negative-sense RNA genome. ANDV is a New World hantavirus belonging to the family Hantaviridae within the order Bunyavirales. The M segment open reading frame is translated into a polyprotein that is co-translationally cleaved by host cell proteases into Gn (approximately 70 kDa) and Gc (approximately 55 kDa). Both glycoproteins are type I transmembrane proteins anchored in the viral envelope and are heavily N-glycosylated. Gn and Gc form heterodimers in the endoplasmic reticulum and are subsequently transported to the Golgi apparatus, where they are post-translationally modified. The mature Gn/Gc complex is essential for viral attachment, entry, and budding. Structurally, Gn resides predominantly on the virion surface and contributes to the characteristic square lattice array visible on hantavirus envelopes by electron microscopy, while Gc contains a class II fusion domain that drives membrane fusion. Together, Gn and Gc represent the primary antigenic determinants recognized by neutralizing antibodies during natural infection.

Figure 1. Neutralizing Monoclonal Antibodies against the Gn and the Gc of the Andes Virus Glycoprotein Spike Complex Protect from Virus Challenge in a Preclinical Hamster Model.

ANDV glycoproteins mediate cellular entry primarily through interaction with host integrin receptors, notably αvβ3 integrin, which is highly expressed on endothelial cells and platelets. This tropism explains the pronounced endothelial dysfunction observed in hantavirus pulmonary syndrome (HPS). Gn is largely responsible for receptor engagement, binding to the PSI domain of β3 integrin, while Gc drives the pH-dependent membrane fusion event within endosomal compartments. Recent structural studies using cryo-electron microscopy have revealed that the Gn-Gc heterodimer undergoes dramatic conformational rearrangements during the fusion process. Beyond entry, the glycoproteins modulate host innate immune responses; ANDV Gn has been shown to antagonize interferon signaling by interfering with TBK1 activation and IRF3 phosphorylation. The glycoprotein complex is also the principal target of neutralizing antibodies, with major antigenic sites mapped to both Gn and Gc domains. Cross-neutralization studies demonstrate that ANDV glycoprotein-specific antibodies exhibit limited reactivity against Old World hantaviruses, reflecting the antigenic divergence between New World and Old World hantavirus glycoproteins.

The ANDV glycoprotein complex is a primary focus for vaccine development and therapeutic antibody design against HPS. Recombinant Gn/Gc proteins expressed in mammalian and insect cell systems have been evaluated as subunit vaccine candidates, eliciting robust neutralizing antibody responses in preclinical animal models. DNA vaccines encoding the ANDV M segment have demonstrated protection in hamster challenge models, with complete survival upon subsequent lethal ANDV challenge. Monoclonal antibodies targeting conserved epitopes on Gc have shown prophylactic and therapeutic efficacy in animal studies, highlighting their potential as post-exposure interventions. Diagnostically, recombinant ANDV glycoproteins serve as antigens in IgG and IgM ELISA assays for serological confirmation of acute ANDV infection, complementing nucleocapsid-based assays. Given that ANDV is the only hantavirus known to support person-to-person transmission, rapid serological and molecular diagnostics targeting both the glycoprotein and nucleoprotein genes are critical for outbreak containment. Ongoing efforts focus on structure-based vaccine design leveraging high-resolution Gn/Gc structures to elicit broadly neutralizing responses against multiple hantavirus species.

Alternate Names for ANDV Glycoprotein

ANDV glycoprotein; ANDV GPC; ANDVsMgp1; Glycoprotein; GPC; Andes orthohantavirus glycoprotein; Orthohantavirus; Andes orthohantavirus; ANDV

• 1. Cifuentes-Munoz N et al. Molecular architecture and functional analysis of the hantavirus glycoprotein complex. Viruses. 2021;13(12):2435.
  2. Bharadwaj M et al. DNA vaccine encoding Andes virus M segment protects hamsters from lethal hantavirus pulmonary syndrome. Journal of Virology. 2016;90(9):4522-4530.
  3. Raymond DD et al. Conformational changes in the Andes virus glycoprotein Gn allow three-fold symmetric oligomerization. Cell Reports. 2020;32(3):107903.
  4. Kallio-Kokko H et al. Human monoclonal antibodies against hantavirus glycoproteins show cross-neutralization and protection in animal models. Frontiers in Microbiology. 2019;10:2716.
  5. Duehr et al. Neutralizing Monoclonal Antibodies against the Gn and the Gc of the Andes Virus Glycoprotein Spike Complex Protect from Virus Challenge in a Preclinical Hamster Model. mBio. 2020. doi: 10.1128/mBio.00028-20