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Ann C. Palmenberg - One of the best experts on this subject based on the ideXlab platform.
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Article No. Vl970126 Topological Organization of Picornaviral Genomes: Statistical Prediction of RNA Structural Signals
2015Co-Authors: Ann C. Palmenberg, Jean-yves SgroAbstract:We have analyzed 11 picornaviral RNA genomic sequences by optimal and suboptimal minimum free energy folding algorithms. The systematic summation of all pairing partners for each base in the suboptimal structures (P-num value) shows a distinct pattern of alternating low and high values when plotted against the sequence length and indicate regions within each genome where secondary structure(s) are likely to play a significant role in virus biology. The individual folds augmented by data from phylogenetic folds, collectively suggest some revisions of existing models for 5'-untranslated regions of Cardioviruses and enteroviruses that might better explain the functions of these regions. ©1997 Academic Press Key Words: mfold; picornavirus; secondary structure prediction; RNA modeling; topology. We are interested in the informational complexity of positive-strand RNA viral genomes and in particular the genomes of the RNA picornaviruses. These genomes range in length from 7100 to 8200 bases, and scattered within are multiple regions of intricate RN
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Leader-induced phosphorylation of nucleoporins correlates with nuclear trafficking inhibition by Cardioviruses
2014Co-Authors: Frederick W. Porter, Ann C. PalmenbergAbstract:Picornaviruses disrupt nucleocytoplasmic trafficking pathways during infection. Poliovirus and rhinovirus inhibit nuclear protein import/export through a series of 2A protease-dependent cleavages within nuclear pore proteins (nucleoporins [Nups]), including Nup62, Nup98, and Nup153. Cardioviruses lack the same protease and instead affect trafficking inhibition through an activity mapped to their leader (L) protein, a 67- to 76-amino acid (aa) polypeptide with no known enzymatic activity. We have shown that L from encephalomyo-carditis virus (EMCV) binds and inhibits the activity of Ran-GTPase, a key regulator of nucleocytoplasmic transport. We now report that recombinant EMCV L triggers the unregulated efflux of protein cargo from preloaded HeLa cell nuclei in cell-free reactions dependent upon Xenopus egg cytosol or HeLa cell-derived cytosol. Recombinant L was the only viral protein necessary for this activity or for nuclear protein import inhibition. Mutational disruption of the L protein zinc finger domain (C19A) abrogated the inhibitory activity for both import and efflux in cell extracts, but mutations in the C-terminal acidic domain of L (aa 37 to 61) did not. Notably, HeLa cell nuclei treated with L, or those from EMCV-infected cells, showed reproducibly altered patterns of nucleoporin phosphorylation. Nup62, Nup153, and Nup214 each became hyperphosphorylated in an L-dependent manner. Staurosporine, a broad-spectrum kinase inhibitor, blocked this phosphorylation and rescued nuclear import/export activity from L-dependent inhibition. Therefore, Cardioviruses target the sam
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AMP-activated protein kinase phosphorylates EMCV, TMEV and SafV leader proteins at different sites.
Virology, 2014Co-Authors: Holly A. Basta, Ann C. PalmenbergAbstract:Cardioviruses of the Encephalomyocarditis virus (EMCV) and Theilovirus species encode small, amino-terminal proteins called Leaders (L). Phosphorylation of the EMCV L (LE) at two distinct sites by CK2 and Syk kinases is important for virus-induced Nup phosphorylation and nucleocytoplasmic trafficking inhibition. Despite similar biological activities, the LE phosphorylation sites are not conserved in the Theiloviruses, Saffold virus (LS, SafV) or Theiler׳s murine encephalitis virus (LT, TMEV) sequences even though these proteins also become phosphorylated in cells and cell-free extracts. Site prediction algorithms, combined with panels of site-specific protein mutations now identify analogous, but not homologous phosphorylation sites in the Ser/Thr and Theilo protein domains of LT and LS, respectively. In both cases, recombinant AMP-activated kinase (AMPK) was reactive with the proteins at these sites, and also with LE, modifying the same residue recognized by CK2.
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Mutational analysis of the EMCV 2A protein identifies a nuclear localization signal and an eIF4E binding site
Virology, 2010Co-Authors: Rachel Groppo, Bradley A. Brown, Ann C. PalmenbergAbstract:Cardioviruses have a unique 2A protein (143 aa). During genome translation, the encephalomyocarditis virus (EMCV) 2A is released through a ribosome skipping event mitigated through C-terminal 2A sequences and by subsequent N-terminal reaction with viral 3Cpro. Although viral replication is cytoplasmic, mature 2A accumulates in nucleoli shortly after infection. Some protein also transiently associates with cytoplasmic 40S ribosomal subunits, an activity contributing to inhibition of cellular cap-dependent translation. Cardiovirus sequences predict an eIF4E binding site (aa 126–134) and a nuclear localization signal (NLS, aa 91–102), within 2A, both of which are functional during EMCV infection. Point mutations preventing eIF4E:2A interactions gave small-plaque phenotype viruses, but still inhibited cellular cap-dependent translation. Deletions within the NLS motif relocalized 2A to the cytoplasm and abrogated the inhibition of cap-dependent translation. A fusion protein linking the 2A NLS to eGFP was sufficient to redirect the reporter to the nucleus but not into nucleoli.
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Leader-Induced Phosphorylation of Nucleoporins Correlates with Nuclear Trafficking Inhibition by Cardioviruses
Journal of virology, 2008Co-Authors: Frederick W. Porter, Ann C. PalmenbergAbstract:Picornaviruses disrupt nucleocytoplasmic trafficking pathways during infection. Poliovirus and rhinovirus inhibit nuclear protein import/export through a series of 2A protease-dependent cleavages within nuclear pore proteins (nucleoporins [Nups]), including Nup62, Nup98, and Nup153. Cardioviruses lack the same protease and instead affect trafficking inhibition through an activity mapped to their leader (L) protein, a 67- to 76-amino acid (aa) polypeptide with no known enzymatic activity. We have shown that L from encephalomyocarditis virus (EMCV) binds and inhibits the activity of Ran-GTPase, a key regulator of nucleocytoplasmic transport. We now report that recombinant EMCV L triggers the unregulated efflux of protein cargo from preloaded HeLa cell nuclei in cell-free reactions dependent upon Xenopus egg cytosol or HeLa cell-derived cytosol. Recombinant L was the only viral protein necessary for this activity or for nuclear protein import inhibition. Mutational disruption of the L protein zinc finger domain (C19A) abrogated the inhibitory activity for both import and efflux in cell extracts, but mutations in the C-terminal acidic domain of L (aa 37 to 61) did not. Notably, HeLa cell nuclei treated with L, or those from EMCV-infected cells, showed reproducibly altered patterns of nucleoporin phosphorylation. Nup62, Nup153, and Nup214 each became hyperphosphorylated in an L-dependent manner. Staurosporine, a broad-spectrum kinase inhibitor, blocked this phosphorylation and rescued nuclear import/export activity from L-dependent inhibition. Therefore, Cardioviruses target the same group of nucleoporins as enteroviruses, but the effector mechanism triggered by L (or L-Ran complexes) involves a unique cytosol-dependent phosphorylation cascade rather than proteolysis. Nuclear pore complexes (NPCs) are massive proteinaceous structures spanning the nuclear envelope and enabling the regulated trafficking of protein and RNA between the cytoplasm and nucleus (31). The NPCs of higher eukaryotes are assembled from about 30 different integral proteins, called nucleoporins (Nups), arranged with eightfold radial symmetry (33). The specificity of protein movement into or out of a nucleus depends on a cargo’s display of a nuclear localization
Thomas Michiels - One of the best experts on this subject based on the ideXlab platform.
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The Leader Protein of Theiler's Virus Prevents the Activation of PKR.
Journal of virology, 2019Co-Authors: Fabian Borghese, Frederic Sorgeloos, Teresa Cesaro, Thomas MichielsAbstract:Leader (L) proteins encoded by Cardioviruses are multifunctional proteins that contribute to innate immunity evasion. L proteins of Theiler's murine encephalomyelitis virus (TMEV), Saffold virus (SAFV), and encephalomyocarditis virus (EMCV) were reported to inhibit stress granule assembly in infected cells. Here, we show that TMEV L can act at two levels in the stress granule formation pathway: on the one hand, it can inhibit sodium arsenite-induced stress granule assembly without preventing eIF2α phosphorylation and, thus, acts downstream of eIF2α; on the other hand, it can inhibit eucaryotic translation initiation factor 2 alpha kinase 2 (PKR) activation and the consequent PKR-mediated eIF2α phosphorylation. Interestingly, coimmunostaining experiments revealed that PKR colocalizes with viral double-stranded RNA (dsRNA) in cells infected with L-mutant viruses but not in cells infected with the wild-type virus. Furthermore, PKR coprecipitated with dsRNA from cells infected with L-mutant viruses significantly more than from cells infected with the wild-type virus. These data strongly suggest that L blocks PKR activation by preventing the interaction between PKR and viral dsRNA. In infected cells, L also rendered PKR refractory to subsequent activation by poly(I·C). However, no interaction was observed between L and either dsRNA or PKR. Taken together, our results suggest that, unlike other viral proteins, L indirectly acts on PKR to negatively regulate its responsiveness to dsRNA.IMPORTANCE The leader (L) protein encoded by Cardioviruses is a very short multifunctional protein that contributes to evasion of the host innate immune response. This protein notably prevents the formation of stress granules in infected cells. Using Theiler's virus as a model, we show that L proteins can act at two levels in the stress response pathway leading to stress granule formation, the most striking one being the inhibition of eucaryotic translation initiation factor 2 alpha kinase 2 (PKR) activation. Interestingly, the leader protein appears to inhibit PKR via a novel mechanism by rendering this kinase unable to detect double-stranded RNA, its typical activator. Unlike other viral proteins, such as influenza virus NS1, the leader protein appears to interact with neither PKR nor double-stranded RNA, suggesting that it acts indirectly to trigger the inhibition of the kinase.
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Innate Immune Detection of Cardioviruses and Viral Disruption of Interferon Signaling.
Frontiers in microbiology, 2018Co-Authors: Eric C. Freundt, Melissa Drappier, Thomas MichielsAbstract:Cardioviruses are members of the Picornaviridae family and infect a variety of mammals, from mice to humans. Replication of Cardioviruses produces double stranded RNA that is detected by helicases in the RIG-I-like receptor family and leads to a signaling cascade to produce type I interferon. Like other viruses within Picornaviridae, however, Cardioviruses have evolved several mechanisms to inhibit interferon production. In this review, we summarize recent findings that have uncovered several proteins enabling efficient detection of cardiovirus dsRNA and discuss which cell types may be most important for interferon production in vivo. Additionally, we describe how cardiovirus proteins L, 3C and L* disrupt interferon production and antagonize the antiviral activity of interferon effector molecules.
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Theiler’s Virus Central Nervous System Infection
The Picornaviruses, 2014Co-Authors: Thomas Michiels, Raymond P. RoosAbstract:The Cardiovirus genus is divided into two species: the Encephalomyocarditis species, which includes encephalomyocarditis virus (EMCV) and mengovirus, and the Theilovirus species, which includes Theiler’s murine encephalomyelitis virus (TMEV), Vilyuisk human encephalomyelitis virus (VHEV), and Saffold virus (SAFV). This chapter discusses members of the Cardiovirus genus and distinctive characteristics of these viruses. It focuses on the pathogenesis of TMEV-induced disease because of the extensive investigations of this topic as well as the remarkable ability of this virus to establish lifelong infection of the central nervous system (CNS) and to produce an immune-mediated demyelinating disease. There are many features of Cardioviruses, and especially TMEV, that make them attractive for pathogenesis studies, including the following: the unusual and rather unique characteristics of TMEV strains and TMEV-induced diseases (neurovirulent versus persistent strains, acute versus chronic disease, virus-induced versus immune-mediated pathology); the ability of some strains to persist in the host in the absence of latency or genome integration; the substantial knowledge concerning Cardioviruses along with powerful tools for their study; the experimental model system of TMEV (and EMCV) infection in the mouse, which is the virus’ natural host. The recent identification of SAFV infection as a frequent one in humans has focused attention on whether this virus causes disease in humans. Furthermore, the identification of the human SAFV indicates that efforts investigating the involvement of Cardioviruses as a cause of Vilyuisk encephalomyelitis should be renewed.
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The Leader Protein of Cardioviruses Inhibits Stress Granule Assembly
Journal of virology, 2011Co-Authors: Fabian Borghese, Thomas MichielsAbstract:Stress granules (SG) are cytoplasmic aggregates of stalled translation preinitiation complexes that form in cells exposed to various environmental stresses. Here, we show that stress granules assemble in cells infected with Theiler's murine encephalomyelitis virus (TMEV) mutants carrying alterations in the leader (L) protein, but not in cells infected with wild-type TMEV. Stress granules also formed in STAT1-deficient cells, suggesting that SG formation was not a consequence of increased type I interferon (IFN) production when cells were infected with the mutant virus. Ectopic expression of the wild-type L protein was sufficient to inhibit stress granule formation induced by sodium arsenite or thapsigargin treatment. In conclusion, TMEV infection induces stress granule assembly, but this process is inhibited by the L protein. Unlike poliovirus-induced stress granules, TMEV-induced stress granules did not contain the nuclear protein Sam68 but contained polypyrimidine tract binding protein (PTB), an internal ribosome entry site (IRES)-interacting protein. Moreover, G3BP was not degraded and was found in SG after TMEV infection, suggesting that SG content could be virus specific. Despite the colocalization of PTB with SG and the known interaction of PTB with viral RNA, in situ hybridization and immunofluorescence assays failed to detect viral RNA trapped in infection-induced SG. Recombinant Theiler's viruses expressing the L protein of Saffold virus 2 (SAFV-2), a closely related human theilovirus, or the L protein of mengovirus, an encephalomyocarditis virus (EMCV) strain, also inhibited infection-induced stress granule assembly, suggesting that stress granule antagonism is a common feature of cardiovirus L proteins.
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Random Mutagenesis Defines a Domain of Theiler's Virus Leader Protein That Is Essential for Antagonism of Nucleocytoplasmic Trafficking and Cytokine Gene Expression
Journal of Virology, 2009Co-Authors: Céline Ricour, Fabian Borghese, Frederic Sorgeloos, Frank J. M. Van Kuppeveld, Stanleyson V Hato, Thomas MichielsAbstract:The leader protein of Cardioviruses, Theiler's murine encephalomyelitis virus (TMEV) and encephalomyocarditis virus (EMCV), is a multifunctional protein known to antagonize type I interferon expression and to interfere with nucleocytoplasmic trafficking of host proteins and mRNA. This protein plays an important role in the capacity of TMEV to establish persistent infection of the central nervous system. Mutant forms of the TMEV leader protein were generated by random mutagenesis and selected after retroviral transduction on the basis of the loss of the highly toxic nature of this protein. Selected mutations define a short C-terminal domain of the leader conserved in TMEV and Saffold virus but lacking in the EMCV leader and thus called the Theilo domain. Mutations in this domain had a dramatic impact on TMEV L protein activity. Like the zinc finger mutation, Theilo domain mutations affected all of the activities of the L protein tested: interferon gene transcription and IRF-3 dimerization antagonism, alteration of nucleocytoplasmic trafficking, nucleoporin 98 hyperphosphorylation, and viral persistence in vivo. This suggests that the Zn finger and the Theilo domain of the protein cooperate for function. Moreover, the fact that all of the activities tested were affected by these mutations suggests that the various leader protein functions are somehow coupled.
Paul L. Hallenbeck - One of the best experts on this subject based on the ideXlab platform.
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Structure of Seneca Valley Virus-001: an oncolytic picornavirus representing a new genus
Structure (London England : 1993), 2008Co-Authors: Sangita Venkataraman, Seshidhar P. Reddy, Jackie Loo, Neeraja Idamakanti, Paul L. Hallenbeck, Vijay S. ReddyAbstract:The crystal structure of Seneca Valley Virus-001 (SVV-001), the representative member of a new genus, Senecavirus, is reported at 2.3A resolution. SVV-001 is the first naturally occurring nonpathogenic picornavirus shown to mediate selective cytotoxicity towards tumor cells with neuroendocrine cancer features. The nonsegmented (+) ssRNA genome of SVV-001 shares closest sequence similarity with the genomes of the members of Cardiovirus. The overall tertiary structure of VP1-VP4 subunits is conserved with the exception of loops, especially those of VP1 that show large deviations relative to the members of the Cardioviruses. The surface loops of VP1 and VP2 are predicted to mediate cell tropism of SVV-001. In addition, the organization of the packaged nucleic acid density indicates that certain regions of VP2 and VP4 interact closely with the packaged nucleic acid.
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complete genome sequence analysis of seneca valley virus 001 a novel oncolytic picornavirus
Journal of General Virology, 2008Co-Authors: Laura M Hales, Seshidhar P. Reddy, Nick J Knowles, Carl Hay, Paul L. HallenbeckAbstract:The complete genome sequence of Seneca Valley virus-001 (SVV-001), a small RNA virus, was determined and was shown to have typical picornavirus features. The 7280 nt long genome was predicted to contain a 5′ untranslated region (UTR) of 666 nt, followed by a single long open reading frame consisting of 6543 nt, which encodes a 2181 aa polyprotein. This polyprotein could potentially be cleaved into 12 polypeptides in the standard picornavirus L-4-3-4 layout. A 3′ UTR of 71 nt was followed by a poly(A) tail of unknown length. Comparisons with other picornaviruses showed that the P1, 2C, 3C and 3D polypeptides of SVV-001 were related most closely to those of the Cardioviruses, although they were not related as closely to those of encephalomyocarditis virus and Theiler's murine encephalomyelitis virus as the latter were to each other. Most other regions of the polyprotein differed considerably from those of all other known picornaviruses. SVV-001 contains elements of an internal ribosome entry site reminiscent of that found in hepatitis C virus and a number of genetically diverse picornaviruses. SVV-001 is a novel picornavirus and it is proposed that it be classified as the prototype species in a novel genus named ‘Senecavirus’.
Mehar Angez - One of the best experts on this subject based on the ideXlab platform.
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Cardioviruses Are Genetically Diverse and Cause Common Enteric Infections in South Asian Children
Journal of virology, 2009Co-Authors: Olga Blinkova, Amit Kapoor, Joseph Victoria, Asif Naeem, Morris S. Jones, Nathan D. Wolfe, S. Shahid Shaukat, Salmaan Sharif, Muhammad Masroor Alam, Mehar AngezAbstract:Cardioviruses cause enteric infections in mice and rats which when disseminated have been associated with myocarditis, type 1 diabetes, encephalitis, and multiple sclerosis-like symptoms. Cardioviruses have also been detected at lower frequencies in other mammals. The Cardiovirus genus within the Picornaviridae family is currently made up of two viral species, Theilovirus and Encephalomyocarditis virus. Until recently, only a single strain of Cardioviruses (Vilyuisk virus within the Theilovirus species) associated with a geographically restricted and prevalent encephalitis-like condition had been reported to occur in humans. A second theilovirus-related cardiovirus (Saffold virus [SAFV]) was reported in 2007 and subsequently found in respiratory secretions from children with respiratory problems and in stools of both healthy and diarrheic children. Using viral metagenomics, we identified RNA fragments related to SAFV in the stools of Pakistani and Afghani children with nonpolio acute flaccid paralysis (AFP). We sequenced three near-full-length genomes, showing the presence of divergent strains of SAFV and preliminary evidence of a distant recombination event between the ancestors of the Theiler-like viruses of rats and those of human SAFV. Further VP1 sequencing showed the presence of five new SAFV genotypes, doubling the reported genetic diversity of human and animal theiloviruses combined. Both AFP patients and healthy children in Pakistan were found to be excreting SAFV at high frequencies of 9 and 12%, respectively. Further studies are needed to examine the roles of these highly common and diverse SAFV genotypes in nonpolio AFP and other human diseases.
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A highly prevalent and genetically diversified Picornaviridae genus in South Asian children
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Amit Kapoor, Joseph Victoria, Asif Naeem, S. Shahid Shaukat, Salmaan Sharif, Muhammad Masroor Alam, Peter Simmonds, Elizabeth Slikas, Thaweesak Chieochansin, Mehar AngezAbstract:Viral metagenomics focused on particle-protected nucleic acids was used on the stools of South Asian children with nonpolio acute flaccid paralysis (AFP). We identified sequences distantly related to Seneca Valley virus and Cardioviruses that were then used as genetic footholds to characterize multiple viral species within a previously unreported genus of the Picornaviridae family. The picornaviruses were detected in the stools of >40% of AFP and healthy Pakistani children. A genetically diverse and highly prevalent enteric viral infection, characteristics similar to the Enterovirus genus, was therefore identified substantially expanding the genetic diversity of the RNA viral flora commonly found in children.
Amit Kapoor - One of the best experts on this subject based on the ideXlab platform.
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EL: Cardioviruses are genetically diverse and cause common enteric infections in South Asian children
2015Co-Authors: Olga Blinkova, Amit Kapoor, Joseph Victoria, Morris Jones, Nathan Wolfe, Asif Naeem, Sohail Zaidi, Eric L. DelwartAbstract:Cardioviruses cause enteric infections in mice and rats which when disseminated have been associated with myocarditis, type 1 diabetes, encephalitis, and multiple sclerosis-like symptoms. Cardioviruses have also been detected at lower frequencies in other mammals. The Cardiovirus genus within the Picornaviridae family is currently made up of two viral species, Theilovirus and Encephalomyocarditis virus. Until recently, only a single strain of Cardioviruses (Vilyuisk virus within the Theilovirus species) associated with a geographically restricted and prevalent encephalitis-like condition had been reported to occur in humans. A second theilovirus-related cardiovirus (Saffold virus [SAFV]) was reported in 2007 and subsequently found in respiratory secretions from children with respiratory problems and in stools of both healthy and diarrheic children. Using viral met-agenomics, we identified RNA fragments related to SAFV in the stools of Pakistani and Afghani children with nonpolio acute flaccid paralysis (AFP). We sequenced three near-full-length genomes, showing the presence of divergent strains of SAFV and preliminary evidence of a distant recombination event between the ancestors of the Theiler-like viruses of rats and those of human SAFV. Further VP1 sequencing showed the presence of five new SAFV genotypes, doubling the reported genetic diversity of human and animal theiloviruses combined
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frequent detection of highly diverse variants of cardiovirus cosavirus bocavirus and circovirus in sewage samples collected in the united states
Journal of Clinical Microbiology, 2009Co-Authors: Olga Blinkova, Amit Kapoor, Karyna Rosario, Linlin Li, Beth Slikas, Flavien BernardinAbstract:Untreated sewage samples from 12 cities in the United States were screened for the presence of recently characterized RNA and DNA viruses found at high prevalence in the stool specimens of South Asian children. Genetic variants of human cosaviruses and Cardioviruses in the Picornaviridae family and of DNA circoviruses and human bocaviruses were detected, expanding the known genetic diversity and geographic range of these newly identified viruses. All four virus groups were detected in sewage samples of less than a milliliter from multiple U.S. cities. PCR screening of particle-protected viral nucleic acid in sewage samples could therefore rapidly establish the presence and determine the diversity of four newly described enteric viruses in large urban populations. More frequent and deeper sampling of viral nucleic acids in sewage samples could be used to monitor changes in the prevalence and genetic composition of these and other novel enteric viruses.
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Cardioviruses Are Genetically Diverse and Cause Common Enteric Infections in South Asian Children
Journal of virology, 2009Co-Authors: Olga Blinkova, Amit Kapoor, Joseph Victoria, Asif Naeem, Morris S. Jones, Nathan D. Wolfe, S. Shahid Shaukat, Salmaan Sharif, Muhammad Masroor Alam, Mehar AngezAbstract:Cardioviruses cause enteric infections in mice and rats which when disseminated have been associated with myocarditis, type 1 diabetes, encephalitis, and multiple sclerosis-like symptoms. Cardioviruses have also been detected at lower frequencies in other mammals. The Cardiovirus genus within the Picornaviridae family is currently made up of two viral species, Theilovirus and Encephalomyocarditis virus. Until recently, only a single strain of Cardioviruses (Vilyuisk virus within the Theilovirus species) associated with a geographically restricted and prevalent encephalitis-like condition had been reported to occur in humans. A second theilovirus-related cardiovirus (Saffold virus [SAFV]) was reported in 2007 and subsequently found in respiratory secretions from children with respiratory problems and in stools of both healthy and diarrheic children. Using viral metagenomics, we identified RNA fragments related to SAFV in the stools of Pakistani and Afghani children with nonpolio acute flaccid paralysis (AFP). We sequenced three near-full-length genomes, showing the presence of divergent strains of SAFV and preliminary evidence of a distant recombination event between the ancestors of the Theiler-like viruses of rats and those of human SAFV. Further VP1 sequencing showed the presence of five new SAFV genotypes, doubling the reported genetic diversity of human and animal theiloviruses combined. Both AFP patients and healthy children in Pakistan were found to be excreting SAFV at high frequencies of 9 and 12%, respectively. Further studies are needed to examine the roles of these highly common and diverse SAFV genotypes in nonpolio AFP and other human diseases.
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A highly prevalent and genetically diversified Picornaviridae genus in South Asian children
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Amit Kapoor, Joseph Victoria, Asif Naeem, S. Shahid Shaukat, Salmaan Sharif, Muhammad Masroor Alam, Peter Simmonds, Elizabeth Slikas, Thaweesak Chieochansin, Mehar AngezAbstract:Viral metagenomics focused on particle-protected nucleic acids was used on the stools of South Asian children with nonpolio acute flaccid paralysis (AFP). We identified sequences distantly related to Seneca Valley virus and Cardioviruses that were then used as genetic footholds to characterize multiple viral species within a previously unreported genus of the Picornaviridae family. The picornaviruses were detected in the stools of >40% of AFP and healthy Pakistani children. A genetically diverse and highly prevalent enteric viral infection, characteristics similar to the Enterovirus genus, was therefore identified substantially expanding the genetic diversity of the RNA viral flora commonly found in children.