Molecular evolution of the VP1, VP2 and VP3 genes in human rhinovirus species C

Kuroda, Makoto; Niwa, Shoichi; Sekizuka, Tsuyoshi; Tsukagoshi, Hiroyuki; Yokoyama, Masahiro; Ryo, Akihide; Sato, Hironori; Kiyota, Naoko; Noda, Masahiro; Kozawa, Kunihisa; Shirabe, Komei; Kusaka, Takashi; Shimojo, Naoki; Hasegawa, Shunji; Sugai, Kazuko; Obuchi, Masatsugu; Tashiro, Masato; Oishi, Kazunori; Ishii, Haruyuki; Kimura, Hirokazu

doi:10.1038/srep08185

Cited by 20 publications

(20 citation statements)

References 32 publications

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“…Near full-length sequences of 14 human rhinovirus strains (strains A through N) were aligned (MUSCLE); a neighbor-joining consensus tree (1,000 replicates) is shown. Full-length reference sequences for rhinovirus A (HRV-A89), rhinovirus B (HRV-B14), and representative fulllength genome sequences from each of the rhinovirus C lineages (GenBank accession numbers EF077280, GQ223227, and JN990702 [40]) were included for comparison. Poliovirus 1 was used as the outgroup.…”

Section: Discussionmentioning

confidence: 99%

Unbiased Detection of Respiratory Viruses by Use of RNA Sequencing-Based Metagenomics: a Systematic Comparison to a Commercial PCR Panel

et al. 2016

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e Current infectious disease molecular tests are largely pathogen specific, requiring test selection based on the patient's symptoms. For many syndromes caused by a large number of viral, bacterial, or fungal pathogens, such as respiratory tract infections, this necessitates large panels of tests and has limited yield. In contrast, next-generation sequencing-based metagenomics can be used for unbiased detection of any expected or unexpected pathogen. However, barriers for its diagnostic implementation include incomplete understanding of analytical performance and complexity of sequence data analysis. We compared detection of known respiratory virus-positive (n ‫؍‬ 42) and unselected (n ‫؍‬ 67) pediatric nasopharyngeal swabs using an RNA sequencing (RNA-seq)-based metagenomics approach and Taxonomer, an ultrarapid, interactive, web-based metagenomics data analysis tool, with an FDA-cleared respiratory virus panel (RVP; GenMark eSensor). Untargeted metagenomics detected 86% of known respiratory virus infections, and additional PCR testing confirmed RVP results for only 2 (33%) of the discordant samples. In unselected samples, untargeted metagenomics had excellent agreement with the RVP (93%). In addition, untargeted metagenomics detected an additional 12 viruses that were either not targeted by the RVP or missed due to highly divergent genome sequences. Normalized viral read counts for untargeted metagenomics correlated with viral burden determined by quantitative PCR and showed high intrarun and interrun reproducibility. Partial or full-length viral genome sequences were generated in 86% of RNA-seq-positive samples, allowing assessment of antiviral resistance, strain-level typing, and phylogenetic relatedness. Overall, untargeted metagenomics had high agreement with a sensitive RVP, detected viruses not targeted by the RVP, and yielded epidemiologically and clinically valuable sequence information. L aboratory diagnosis of infectious diseases has historically taken a syndrome-based approach. Culture of appropriate specimens on a combination of relevant media or cell lines enables detection of certain common bacterial, viral, and fungal pathogens. However, culture requires experienced personnel, requires several days to weeks to yield a definitive answer, depends on viability and appropriate culture conditions, and has limited sensitivity. Molecular tests have superior turnaround times, sensitivity, and taxonomic resolution. However, only targeted pathogens can be detected, and differentiation of clinically or epidemiologically relevant strains or genotypes is limited. Moreover, molecular tests need to be updated when new species or strains are recognized to ensure that newly identified genetic variants can be detected.In contrast, next-generation sequencing-based metagenomic testing combines and extends many advantages of molecular tests and culture-based methods. Host-and pathogen-derived nucleic acids are sequenced without a priori knowledge of expected pathogens, allowing simultaneous detection of a virtually ...

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Section: Discussionmentioning

confidence: 99%

Unbiased Detection of Respiratory Viruses by Use of RNA Sequencing-Based Metagenomics: a Systematic Comparison to a Commercial PCR Panel

et al. 2016

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“…Scores obtained for individual sites ranged from 0.007 to 1.683 bits, with an average score of 0.16 bit, indicating that Gag-CA diversity in the subtype B population is relatively small, as seen in many viral enzymes (36)(37)(38). This is in contrast to virion surface proteins, for which entropy scores often exceeded 2.0 bits, reaching close to a maximum value of 4.4 bits in the antigenic sites (34,39,40).…”

Section: Virus Particle Production In H9 Cells Bcmentioning

confidence: 98%

Allosteric Regulation of HIV-1 Capsid Structure for Gag Assembly, Virion Production, and Viral Infectivity by a Disordered Interdomain Linker

Koma

Kotani

Miyakawa

et al. 2019

J Virol

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The retroviral Gag capsid (Gag-CA) interdomain linker is an unstructured peptide segment connecting structured N-terminal and C-terminal domains. Although the region is reported to play roles in virion morphogenesis and infectivity, underlying molecular mechanisms remain unexplored. To address this issue, we determined biological and molecular phenotypes of HIV-1 CA linker mutants by experimental and in silico approaches. Among the nine linker mutants tested, eight exhibited attenuation of viral particle production to various extents mostly in parallel with a reduction in viral infectivity. Sucrose density gradient, confocal microscopy, and live-cell protein interaction analyses indicated that the defect is accompanied by attenuation of Gag-Gag interactions following Gag plasma membrane targeting in the cells. In silico analyses revealed distinct distributions of interaction-prone hydrophobic patches between immature and mature CA proteins. Molecular dynamics simulations predicted that the linker mutations can allosterically alter structural fluctuations, including the interaction surfaces apart from the mutation sites in both the immature and mature CA proteins. These results suggest that the HIV-1 CA interdomain linker is a cis-modulator of the CA interaction surfaces to optimize efficiency of Gag assembly, virion production, and viral infectivity. IMPORTANCE HIV-1 particle production and infection are highly ordered processes. Viral Gag proteins play a central role in the assembly and disassembly of viral molecules. Of these, capsid protein (CA) is a major contributor to the Gag-Gag interactions. CA consists of two structured domains, i.e., N-terminal (NTD) and C-terminal (CTD) domains, connected by an unstructured domain named the interdomain linker. While multiple regions in the NTD and CTD are reported to play roles in virion morphogenesis and infectivity, the roles of the linker region in Gag assembly and virus particle formation remain elusive. In this study, we showed by biological and molecular analyses that the linker region functions as an intramolecular modulator to tune Gag assembly, virion production, and viral infectivity. Our study thus illustrates a hitherto-unrecognized mechanism, an allosteric regulation of CA structure by the disordered protein element, for HIV-1 replication.

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“…The capsid is composed of four proteins: VP1, VP2, VP3, and VP4. 4,19 VP4 is on the inside of the virus and anchors the RNA core to the viral capsid. The complete sequencing of all known HRV genomes has been reported.…”

Section: Rhinoviruses Virologymentioning

confidence: 99%

“…A few HRVs used heparin sulfate proteoglycan as an additional receptor and approximately 10 serotypes use low-density lipoprotein as the cell receptor (minor group). In 2002, a new clade of HRVs was reported and labeled HRV-C. 19 Although HRV-C strains have been characterized by genome sequencing, the receptor used to infect epithelial cells is currently unidentified.…”

Section: Rhinoviruses Virologymentioning

confidence: 99%

Update on Human Rhinovirus and Coronavirus Infections

Greenberg

2016

Semin Respir Crit Care Med

117

135

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Human rhinovirus (HRV) and coronavirus (HCoV) infections are associated with both upper respiratory tract illness ("the common cold") and lower respiratory tract illness (pneumonia). New species of HRVs and HCoVs have been diagnosed in the past decade. More sensitive diagnostic tests such as reverse transcription-polymerase chain reaction have expanded our understanding of the role these viruses play in both immunocompetent and immunosuppressed hosts. Recent identification of severe acute respiratory syndrome and Middle East respiratory syndrome viruses causing serious respiratory illnesses has led to renewed efforts for vaccine development. The role these viruses play in patients with chronic lung disease such as asthma makes the search for antiviral agents of increased importance.

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Molecular evolution of the VP1, VP2 and VP3 genes in human rhinovirus species C

Cited by 20 publications

References 32 publications

Unbiased Detection of Respiratory Viruses by Use of RNA Sequencing-Based Metagenomics: a Systematic Comparison to a Commercial PCR Panel

Unbiased Detection of Respiratory Viruses by Use of RNA Sequencing-Based Metagenomics: a Systematic Comparison to a Commercial PCR Panel

Allosteric Regulation of HIV-1 Capsid Structure for Gag Assembly, Virion Production, and Viral Infectivity by a Disordered Interdomain Linker

Update on Human Rhinovirus and Coronavirus Infections

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