Cellular Host Receptors of Arboviruses Causing Hemorrhagic Fever: scientific Review
DOI:
https://doi.org/10.63939/w24zc577Keywords:
Arboviruses, hemorrhagic fever, Host Receptors, Arthropod-borne viruses, Arboviruses ligand-receptors.Abstract
Arboviruses that cause hemorrhagic fever are a wide range of RNA viruses that are mostly spread by insects and other arthropods. How well they interact with certain cellular receptors determines how well they can infect human host cells. Recent research has identified several novel cellular host receptors utilized by different arboviruses to penetrate target cells, a process essential for viral replication and subsequent pathogenesis. The human transferrin receptor 1 (TfR1) is very important for New World clade B arenaviruses, which cause hemorrhagic fevers, to get in. Pathogenic arenaviruses, including Machupo and Junin viruses, exploit human TfR1, whereas closely related nonpathogenic viruses utilize TfR1 orthologs from their natural reservoir hosts. Changes in TfR1 can make it easier or harder for someone to get sick. This means that zoonotic diseases could happen if the host receptor changes.
Viral glycoproteins Gn and Gc help the virus attach to host cells. Clathrin helps CCHFV get into cells. Cholesterol and pH levels can affect this process. Nucleolin on the surface of host cells and DC-SIGN lectin on dendritic cells may also be involved. These interactions facilitate the infection of macrophages, dendritic cells, and epithelial cells, which are crucial for viral dissemination and immune evasion. Several types of receptors have been linked to other arboviruses, such as dengue virus (DENV), West Nile virus (WNV), and others that cause symptoms of hemorrhagic disease. These include Fc gamma receptors (FcγRs), which help antibody-dependent enhancement, different types of lectins like C-type lectins (DC-SIGN), integrins (αvβ3 integrin), laminin receptors, and glycosaminoglycans like heparan sulfate. These receptors often enable viral adherence and invasion of immune or endothelial cells, thereby affecting viral tropism and hemorrhagic pathogenesis.
The redundancy and diversity of receptor molecules employed by arboviruses highlight the complexity of virus-host cell interactions and suggest evolutionary adaptations that facilitate spillover and the emergence of diseases. Understanding these new cellular receptors is important for coming up with antiviral strategies that can stop viruses from getting into cells. However, targeting these receptors is risky because of their normal functions.
New cellular host receptors for arboviruses that cause hemorrhagic fever include human transferrin receptor 1 for New World arenaviruses, clathrin-mediated entry receptors possibly involving nucleolin and DC-SIGN for Crimean-Congo Hemorrhagic Fever Virus, and various Fc receptors, lectins, integrins, laminin receptors, and glycosaminoglycans for flaviviruses and other arboviruses. These findings improve the molecular understanding of hemorrhagic fever virus entry and pathogenesis, presenting both opportunities and challenges for therapeutic intervention.
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