Hantavirus Replication Cycle—An Updated Structural Virology Perspective

Abstract

Hantaviruses infect a wide range of hosts including insectivores and rodents and can also cause zoonotic infections in humans, which can lead to severe disease with possible fatal outcomes. Hantavirus outbreaks are usually linked to the population dynamics of the host animals and their habitats being in close proximity to humans, which is becoming increasingly important in a globalized world. Currently there is neither an approved vaccine nor a specific and effective antiviral treatment available for use in humans. Hantaviruses belong to the order Bunyavirales with a tri-segmented negative-sense RNA genome. They encode only five viral proteins and replicate and transcribe their genome in the cytoplasm of infected cells. However, many details of the viral amplification cycle are still unknown. In recent years, structural biology methods such as cryo-electron tomography, cryo-electron microscopy, and crystallography have contributed essentially to our understanding of virus entry by membrane fusion as well as genome encapsidation by the nucleoprotein. In this review, we provide an update on the hantavirus replication cycle with a special focus on structural virology aspects.

Comprehensive computational analysis reveals YXXΦ[I/L/M/F/V] motif and YXXΦ-like tetrapeptides across HFRS causing Hantaviruses and their association with viral pathogenesis and host immune regulation

“…Nucleoproteins express in the cytoplasm of infected cell ( 56 ). Hantavirus nucleoprotein controls viral replication and assembly, encapsidates viral RNA, and plays a crucial part in the virus life cycle ( 57 ). Consequently, various diagnostics methods have now been developed based on recognizing the hantaviruses nucleoprotein or an anti-nucleoprotein antibody to halt the pathogenesis of viral infection at early stages ( 58 , 59 ).…”

An algal lectin griffithsin inhibits Hantaan virus infection in vitro and in vivo

“…HTNV contains four possible sites for N -linked glycosylation on Gn and one on Gc ( Figure 1 ) ( Schmaljohn et al., 1987 ; Antic et al., 1992 ; Shi and Elliott, 2004 ). Four dimers of Gn and Gc form the core building blocks of the viral spike, which covers the entire surface of the virion ( Hepojoki et al., 2010 ; Huiskonen et al., 2010 ; Meier et al., 2021 ). This suggests that GRFT may effectively inhibit HTNV infection.…”

“…The structure of HTNV GPC was modeled based on the structure of the Andes virus (ANDV) (PDB: 6Y5F) using the SWISS-MODEL program ( Meier et al., 2021 ). The location of each N -linked glycosylation site was indicated except for N399, which is truncated from the original structure.…”

“…HTNV has a tripartite genome consisting of L, M, and S segments encoding RNA-dependent RNA polymerase (RdRp/LP), glycoprotein precursor (GPC), and nucleocapsid protein (NP), respectively ( Vaheri et al., 2013 ; Muyangwa et al., 2015 ). Upon maturation, GPC is processed into Gn and Gc, which form a tetrameric Gn/Gc spike embedded within the viral membrane envelope ( Meier et al., 2021 ). Gn/Gc tetramer is crucial to initiating HTNV attachment and subsequent cell entry ( Serris et al., 2020 ).…”

Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirus

“…Various pathogenesis has been suggested, including immune-mediated cell injury, cytokine storm, and high VEGF responses from intercellular junctions resulting from the virus-integrin interactions (4). Since the majority of deaths are caused by cardiac failure and hypoperfusion rather than hypoxia, several researchers prefer the term "hantavirus cardiopulmonary syndrome" rather than hantavirus pulmonary syndrome (5). No specific drug has been discovered to treat Sin Nombre infection; however, ribavirin, a broad-spectrum antiviral agent, is mainly used for supportive therapy for the treatment of HCPS, but no effective results are reported yet.…”