Bunyavirus N: eIF4F surrogate and cap-guardian

Panganiban, Antonito T.; Mir, Mohammad A.

doi:10.4161/cc.8.9.8315

Cited by 20 publications

(25 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Equally plausible is the existence of an HCMVencoded protein or protein complex that facilitates the recruitment of ribosomes to viral transcripts. For example, the N protein of bunyavirus is capable of replacing the entire eIF4F complex in the translation of viral mRNAs (46). If viral proteins contribute to HCMV mRNA translation, these factors would be excellent candidates for novel antiviral therapeutics, since they would specifically limit viral protein synthesis while leaving host protein synthesis intact.…”

Section: Discussionmentioning

confidence: 99%

Differential Role for Host Translation Factors in Host and Viral Protein Synthesis during Human Cytomegalovirus Infection

Lenarcic

Ziehr

Leon

et al. 2014

J Virol

View full text Add to dashboard Cite

The host eIF4F translation initiation complex plays a critical role the translation of capped mRNAs. Although human cytomegalovirus (HCMV) infection increases the abundance and activity of the host eIF4F complex, the requirement for eIF4F components in HCMV replication and mRNA translation has not been directly tested. In this study, we found that decreasing the abundance or activity of eIF4F from the start of infection inhibits HCMV replication. However, as infection progresses, viral mRNA translation and replication becomes increasingly resistant to eIF4F inhibition. During the late stage of infection the association of representative immediate-early, early, and late mRNAs with polysomes was not affected by eIF4F disruption. In contrast, eIF4F inhibition decreased the translation of representative host eIF4F-dependent mRNAs during the late stage of infection. A global analysis of the translation efficiency of HCMV mRNAs during the late stage of infection found that eIF4F disruption had a minimal impact on the association of HCMV mRNAs with polysomes but significantly diminished the translation efficiency of eIF4F-dependent host transcripts. Together, our data show that the translation of host eIF4F-dependent mRNAs remains dependent on eIF4F activity during HCMV infection. However, during the late stage of infection the translation efficiency of viral mRNAs does not correlate with the abundance or activity of the host eIF4F complex.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential Role for Host Translation Factors in Host and Viral Protein Synthesis during Human Cytomegalovirus Infection

Lenarcic

Ziehr

Leon

et al. 2014

J Virol

View full text Add to dashboard Cite

show abstract

“…The conformationally altered N with a capped primer loaded at the cap-binding site specifi cally binds the nine conserved 3 ¢ nucleotides of vRNA and assists the bound primer to anneal at the 3 ¢ terminus, thus promoting transcription initiation by the hantavirus RdRp. Therefore, the bunyavirus N protein perhaps assumes a functional role similar to that of PB2 of the FluA (Panganiban and Mir 2009 ) .…”

Section: Viral Rna Transcriptionmentioning

confidence: 99%

“…Subsequently, the N protein unwinds and dissociates the panhandle, while remains attached to the 5 ¢ end of the viral RNA. The cleaved nonviral capped primer is then base-paired to the viral RNA template, and the viral polymerase L proceeds with elongation until it reaches the transcription termination signal (Panganiban and Mir 2009 ) .…”

Section: Viral Rna Transcriptionmentioning

confidence: 99%

Bunyavirus: Structure and Replication

Guu

Zheng

Tao

2011

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

The Bunyaviridae family is comprised of a large number of negative-sense, single-stranded RNA viruses that infect animals, insects, and plants. The tripartite genome of bunyaviruses, encapsidated in the form of individual ribonucleoprotein complexes, encodes four structural proteins, the glycoproteins Gc and Gn, the nucleoprotein N, and the viral polymerase L. Some bunyaviruses also use an ambi-sense strategy to encode the nonstructural proteins NSs and NSm. While some bunyaviruses have a T = 12 icosahedral symmetry, others only have locally ordered capsids, or capsids with no detectable symmetry. Bunyaviruses enter cells through clathrin-mediated endocytosis or phagocytosis. In endosome, viral glycoproteins facilitate membrane fusion at acidic pH, thus allowing bunyaviruses to uncoat and deliver their genomic RNA into host cytoplasm. Bunyaviruses replicate in cytoplasm where the viral polymerase L catalyzes both transcription and replication of the viral genome. While transcription requires a cap primer for initiation and ends at specific termination signals before the 3' end of the template is reached, replication copies the entire template and does not depend on any primer for initiation. This review will discuss some of the most interesting aspects of bunyavirus replication, including L protein/N protein-mediated cap snatching, prime-and-realign for transcription and replication initiation, translation-coupled transcription, sequence/secondary structure-dependent transcription termination, ribonucleoprotein encapsidation, and N protein-mediated initiation of viral protein translation. Recent developments on the structure and functional characterization of the bunyavirus capsid and the RNA synthesis machineries (including both protein L and N) will also be discussed.

show abstract

“…Among all viral gene products, the importance of N is underscored by its involvement during many stages of the RVFV replication cycle. N is an RNA binding protein that plays important roles during transcription, translation, replication, and encapsidation of the viral genome into virions (10)(11)(12)(13)(14)(15). During replication, N monomers bind along the entire length of the viral genome and antigenome.…”

mentioning

confidence: 99%

Inhibition of Rift Valley Fever Virus Replication and Perturbation of Nucleocapsid-RNA Interactions by Suramin

Ellenbecker

Lanchy

Lodmell

2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Rift Valley fever virus (RVFV) is an emerging infectious pathogen that causes severe disease in humans and livestock and has the potential for global spread. There are currently no proven safe and effective treatment options for RVFV infection. Inhibition of RNA binding to RVFV nucleocapsid protein (N) represents an attractive antiviral therapeutic strategy because several essential steps in the RVFV replication cycle involve N binding to viral RNA. In this study, we demonstrate the therapeutic potential of the drug suramin by showing that it functions well as an inhibitor of RVFV replication at multiple stages in human cell culture. Suramin has been used previously to treat trypanosomiasis in Africa. We characterize the dynamic and cooperative nature of N-RNA binding interactions and the dissociation of high-molecular-mass ribonucleoprotein complexes using suramin, which we previously identified as an N-RNA binding inhibitor in a high-throughput screen. Finally, we elucidate the molecular mechanism used by suramin in vitro to disrupt both specific and nonspecific binding events important for ribonucleoprotein formation. Rift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus (genus Phlebovirus) that causes severe disease in humans and ruminant livestock. In humans, disease symptoms can range from a mild flu-like illness to hemorrhagic fever, encephalitis, neurological disorders, and blindness (1). Pregnant livestock are at risk for miscarriage, and high mortality rates among newborn animals have been reported (2-4). RVFV can be transmitted by a diverse set of mosquito species, and outbreaks have been more severe outside the historically defined areas of endemicity of sub-Saharan Africa. The potential for RVFV to cause devastating epidemics worldwide is evidenced by its classification as a category A high-priority disease agent by the National Institute for Allergy and Infectious Diseases (NIAID) (5, 6). There are currently no proven safe and effective treatment options for RVFV-infected people or livestock. Increasing our understanding of the basic molecular virology of this important pathogen represents an essential step toward identification of new drug targets and the development of more efficacious antiviral therapeutic compounds.The single-stranded RNA genome of RVFV is composed of three segments (L, M, and S) that appear circular by electron microscopy due to complementarity between the 5=-and 3=-terminal regions (7). The L segment encodes the RNA-dependent RNA polymerase responsible for transcription and replication of the viral genome. The M segment encodes glycoproteins (Gn and Gc) involved in entry into the host cell and nonstructural proteins NSm and 78-kDa protein (8). The S segment utilizes an ambisense strategy to encode the nucleocapsid (N) and NSs proteins, while the genes of the M and L segments are in the negative sense (9). Among all viral gene products, the importance of N is underscored by its involvement during many stages of the RVFV replication cycle. N is an RNA binding prot...

show abstract

Bunyavirus N: eIF4F surrogate and cap-guardian

Cited by 20 publications

References 58 publications

Differential Role for Host Translation Factors in Host and Viral Protein Synthesis during Human Cytomegalovirus Infection

Differential Role for Host Translation Factors in Host and Viral Protein Synthesis during Human Cytomegalovirus Infection

Bunyavirus: Structure and Replication

Inhibition of Rift Valley Fever Virus Replication and Perturbation of Nucleocapsid-RNA Interactions by Suramin

Contact Info

Product

Resources

About