How hantaviruses modulate cellular pathways for efficient replication

Hussein, Islam T. M.; Mir, Mohammad A.

doi:10.2741/e604

Cited by 6 publications

(3 citation statements)

References 111 publications

(63 reference statements)

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“…For example, N has been suggested to play crucial roles in the cap-snatching mechanism of viral transcription initiation and preferential translation of viral mRNAs in infected cells [13, 15]. In addition, N has also been reported to directly interact with viral RdRp, actin filaments, apoptosis enhancers and components of SUMO-1 (small ubiquitin-like modifiers) pathway (reviewed in [31]). N must contain multifunctional domains to perform a series of diverse functions in the host cell during virus replication.…”

Section: Resultsmentioning

confidence: 99%

Ribosomal protein S19-binding domain provides insights into hantavirus nucleocapsid protein-mediated translation initiation mechanism

Ganaie

Haque

Cheng

et al. 2014

Biochemical Journal

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The hantaviral zoonotic diseases pose significant threat to human health due to the lack of potential antiviral therapeutics or a vaccine against hantaviruses. Sin Nombre hantavirus nucleocapsid protein (N) augments mRNA translation. N binds to both the mRNA 5′ cap and 40S ribosomal subunit via ribosomal protein S19 (RPS19). N with the assistance of viral mRNA 5′ untranslated region (UTR) preferentially favors the translation of downstream open reading frame. We identified and characterized the RPS19 binding domain at the N-terminus of N. Its deletion did not influence the secondary structure but impacted the conformation of trimeric N molecules. N variant lacking the RPS19 binding region was able to bind both the mRNA 5′ cap and panhandle like structure, formed by the termini of viral genomic RNA. In addition, N variant formed stable trimers similar to wild type N. Use of this variant in multiple experiments provided insights into the mechanism of ribosome loading during N-mediated translation strategy. Our studies suggest that N molecules individually associated with mRNA 5′ cap and RPS19 of the 40S ribosomal subunit undergo N-N interaction to facilitate the engagement of N associated ribosomes at the mRNA 5′ cap. These studies have revealed new targets for therapeutic intervention of hantavirus infection.

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Section: Resultsmentioning

confidence: 99%

Ribosomal protein S19-binding domain provides insights into hantavirus nucleocapsid protein-mediated translation initiation mechanism

Ganaie

Haque

Cheng

et al. 2014

Biochemical Journal

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“…Hantaviruses, on the other hand, do not induce host translational shutoff and some do not even encode the NSs gene. The N protein of hantaviruses functions as a surrogate for the eIF4F complex (eIF4A, eIF4G, and eIF4F), and thus recruits capped mRNA from the host to initiate viral translation [ 114 ]. Further study will be required to understand bunyavirus NSs functions regulating host and viral protein synthesis.…”

Section: Rvfv and Tosv Nss Protein Promotes Posttranslational Degradamentioning

confidence: 99%

Rift Valley fever virus NSs protein functions and the similarity to other bunyavirus NSs proteins

Ikegami

2016

Virol J

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Rift Valley fever is a mosquito-borne zoonotic disease that affects both ruminants and humans. The nonstructural (NS) protein, which is a major virulence factor for Rift Valley fever virus (RVFV), is encoded on the S-segment. Through the cullin 1-Skp1-Fbox E3 ligase complex, the NSs protein promotes the degradation of at least two host proteins, the TFIIH p62 and the PKR proteins. NSs protein bridges the Fbox protein with subsequent substrates, and facilitates the transfer of ubiquitin. The SAP30-YY1 complex also bridges the NSs protein with chromatin DNA, affecting cohesion and segregation of chromatin DNA as well as the activation of interferon-β promoter. The presence of NSs filaments in the nucleus induces DNA damage responses and causes cell-cycle arrest, p53 activation, and apoptosis. Despite the fact that NSs proteins have poor amino acid similarity among bunyaviruses, the strategy utilized to hijack host cells are similar. This review will provide and summarize an update of recent findings pertaining to the biological functions of the NSs protein of RVFV as well as the differences from those of other bunyaviruses.

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“…Compared to non-pathogenic strains, pathogenic hantaviruses significantly alter the transcriptional activity of many cellular genes ( 18 , 19 ). Recent studies provide solid evidence that hantaviruses’ nucleocapsid proteins have a key role in virus transcription, replication, and assembly ( 20 , 21 ). The nucleoprotein, encoded by the S segment, of hantaviruses consist of 429 to 433 amino acids ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of codon usage pattern and influencing factors in HFRS-causing hantaviruses

et al. 2023

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Hemorrhagic fever with renal syndrome (HFRS) is an acute viral zoonosis carried and transmitted by infected rodents through urine, droppings, or saliva. The etiology of HFRS is complex due to the involvement of viral factors and host immune and genetic factors which hinder the development of potential therapeutic solutions for HFRS. Hantaan virus (HTNV), Dobrava-Belgrade virus (DOBV), Seoul virus (SEOV), and Puumala virus (PUUV) are predominantly found in hantaviral species that cause HFRS in patients. Despite ongoing prevention and control efforts, HFRS remains a serious economic burden worldwide. Furthermore, recent studies reported that the hantavirus nucleocapsid protein is a multi-functional protein and plays a major role in the replication cycle of the hantavirus. However, the precise mechanism of the nucleoproteins in viral pathogenesis is not completely understood. In the framework of the current study, various in silico approaches were employed to identify the factors influencing the codon usage pattern of hantaviral nucleoproteins. Based on the relative synonymous codon usage (RSCU) values, a comparative analysis was performed between HFRS-causing hantavirus and their hosts, suggesting that HTNV, DOBV, SEOV, and PUUV, were inclined to evolve their codon usage patterns that were comparable to those of their hosts. The results indicated that most of the overrepresented codons had AU-endings, which revealed that mutational pressure is the major force shaping codon usage patterns. However, the influence of natural selection and geographical factors cannot be ignored on viral codon usage bias. Further analysis also demonstrated that HFRS causing hantaviruses adapted host-specific codon usage patterns to sustain successful replication and transmission chains within hosts. To our knowledge, no study to date reported the factors influencing the codon usage pattern within hantaviral nucleoproteins. Thus, the proposed computational scheme can help in understanding the underlying mechanism of codon usage patterns in HFRS-causing hantaviruses which lend a helping hand in designing effective anti-HFRS treatments in future. This study, although comprehensive, relies on in silico methods and thus necessitates experimental validation for more solid outcomes. Beyond the identified factors influencing viral behavior, there could be other yet undiscovered influences. These potential factors should be targets for further research to improve HFRS therapeutic strategies.

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How hantaviruses modulate cellular pathways for efficient replication

Cited by 6 publications

References 111 publications

Ribosomal protein S19-binding domain provides insights into hantavirus nucleocapsid protein-mediated translation initiation mechanism

Ribosomal protein S19-binding domain provides insights into hantavirus nucleocapsid protein-mediated translation initiation mechanism

Rift Valley fever virus NSs protein functions and the similarity to other bunyavirus NSs proteins

Identification and characterization of codon usage pattern and influencing factors in HFRS-causing hantaviruses

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