David Schnurr

Publications of David Schnurr

• Toward an integrated human adenovirus designation system that utilizes molecular and serological data and serves both clinical and fundamental virology.

  Authors: Koki Aoki, Mária Benkö, Andrew J Davison, Marcela Echavarria, Dean D Erdman, Balázs Harrach, Adriana E Kajon, David Schnurr, Göran Wadell

  Journal of virology. 03/2011; 85(11):5703-4.

  The following proposals contribute towards elaborating a robust system for designating human adenovirus (HAdV) types....

• Quantitative real-time PCR for rhinovirus, and its use in determining the relationship between TCID50 and the number of viral particles.

  Authors: Lorne A Sachs, David Schnurr, Shigeo Yagi, Marrah E Lachowicz-Scroggins, Jonathan H Widdicombe

  Journal of virological methods. 11/2010; 171(1):212-8.

  The development of a quantitative real-time PCR (qPCR) assay for human rhinovirus serotype 16 (HRV16) is described using the plasmid pR16.11, which contains the full-length genome of HRV16. AThe development of a quantitative real-time PCR (qPCR) assay for human rhinovirus serotype 16 (HRV16) is described using the plasmid pR16.11, which contains the full-length genome of HRV16. A standard curve was generated by plotting the critical threshold (C(t)) against numbers of plasmid. The limit of sensitivity was less than10 cDNA copies, and the curve showed a high degree of linearity over a range of 10(1) to 10(6) cDNA copies with r(2)≥0.9989. Amplification efficiency of the qPCR was greater than 97.6 percent. The standard curve was highly reproducible with low intra- and inter-assay coefficients of variation. Standard curves were also generated from cDNA derived from two viral suspensions of known TCID(50), and were exactly parallel to those generated from the plasmid. Comparison of the curves generated from the plasmid or viral cDNA showed that for the two suspensions, TCID(50) corresponded to either 142 or 2088 viral particles. This new qPCR will permit quantitative assessments of interactions between virus and epithelium such as determinations of the affinity and number of viral binding sites or of the number of virus produced per infected cell.

• Computational analysis of human adenovirus serotype 18.

  Authors: Michael P Walsh, Jason Seto, Damaris Tirado, James Chodosh, David Schnurr, Donald Seto, Morris S Jones

  Virology. 09/2010; 404(2):284-92.

  The genome of the sole remaining unsequenced member of species A, human adenovirus type 18 (HAdV-A18), has been sequenced and analyzed. Members of species A are implicated as gastrointestinalThe genome of the sole remaining unsequenced member of species A, human adenovirus type 18 (HAdV-A18), has been sequenced and analyzed. Members of species A are implicated as gastrointestinal pathogens and were shown to be tumorigenic in rodents. These whole genome and in silico proteome data are important as references for reexamining and integrating earlier work and observations based on lower resolution techniques, such as restriction enzyme digestion patterns, particularly for hypotheses based on pre-genomics data. Additionally, the genome of HAdV-A18 will also serve as reference for current studies examining the molecular evolution and origins of human and simian adenoviruses, particularly genome recombination studies. Applications of this virus as a potential vector for gene delivery protocols may be practical as data accumulate on this and other adenovirus genomes.

• Molecular epidemiology and brief history of emerging adenovirus 14-associated respiratory disease in the United States.

  Authors: Adriana E Kajon, Xiaoyan Lu, Dean D Erdman, Janice Louie, David Schnurr, Kirsten St George, Marion P Koopmans, Taslim Allibhai, David Metzgar

  The Journal of infectious diseases. 07/2010; 202(1):93-103.

  First isolated in the Netherlands in 1955 during an outbreak of acute respiratory disease (ARD) among military recruits, human adenovirus 14 (HAdV-14) has historically been considered rare. With noFirst isolated in the Netherlands in 1955 during an outbreak of acute respiratory disease (ARD) among military recruits, human adenovirus 14 (HAdV-14) has historically been considered rare. With no precedent of circulation in North America, HAdV-14 has been isolated from military and civilian cases of ARD of variable severity since 2003 in the United States. Ninety-nine isolates from military and civilian cases from different geographic locations and circulation periods were characterized by restriction enzyme analysis of viral DNA and select gene sequencing. All examined viruses were found to be identical and to belong to a new genome type designated "HAdV-14p1" (formerly known as "14a"). Comparative alignments of E1A, hexon, and fiber gene sequences with other subspecies B2 HAdVs suggest that HAdV-14p1, like the closely related HAdV-11a, arose from recombination among similar HAdV-11 and HAdV-14 ancestral strains. A deletion of 2 amino acids in the knob region of the fiber protein is the only identified unique characteristic of HAdV-14p1. The current geographic distribution of HAdV-14p1 involves at least 15 states in the Unites States. The role of the fiber mutations in the recent emergence of HAdV-14p1 ARD in North America warrants further study.

• Increased Activity of Coxsackievirus B1 Strains Associated with Severe Disease among Young Infants in the United States, 2007-2008.

  Authors: Mary E Wikswo, Nino Khetsuriani, Ashley L Fowlkes, Xiaotian Zheng, Silvia Peñaranda, Natasha Verma, Stanford T Shulman, Kanta Sircar, Christine C Robinson, Terry Schmidt, David Schnurr, M Steven Oberste

  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 10/2009; 49(5):e44-51.

  BACKGROUND: Enterovirus infections are very common and typically cause mild illness, although neonates are at higher risk for severe illness. In 2007, the Centers for Disease Control and PreventionBACKGROUND: Enterovirus infections are very common and typically cause mild illness, although neonates are at higher risk for severe illness. In 2007, the Centers for Disease Control and Prevention (CDC) received multiple reports of severe neonatal illness and death associated with coxsackievirus B1 (CVB1), a less common enterovirus serotype not previously associated with death in surveillance reports to the CDC. METHODS: This report includes clinical, epidemiologic, and virologic data from cases of severe neonatal illness associated with CVB1 reported during the period from 2007 through 2008 to the National Enterovirus Surveillance System (NESS), a voluntary, passive surveillance system. Also included are data on additional cases reported to the CDC outside of the NESS. Virus isolates or original specimens obtained from patients from 25 states were referred to the CDC picornavirus laboratory for molecular typing or characterization. RESULTS: During 2007-2008, the NESS received 1079 reports of enterovirus infection. CVB1 accounted for 176 (23%) of 775 reported cases with known serotype, making it the most commonly reported serotype for the first time ever in the NESS. Six neonatal deaths due to CVB1 infection were also reported to the CDC during that time. Phylogenetic analysis of the 2007 and 2008 CVB1 strains indicated that the increase in cases resulted from widespread circulation of a single genetic lineage that had been present in the United States since at least 2001. CONCLUSIONS: Healthcare providers and public health departments should be vigilant to the possibility of continuing CVB1-associated neonatal illness, and testing and continued reporting of enterovirus infections should be encouraged.

• Monoclonal Antibodies to VP1 Recognize a Broad Range of Enteroviruses.

  Authors: Lynn Yihong Miao, Christina Pierce, Jennifer Gray-Johnson, Jill Delotell, Carl Shaw, Nate Chapman, Elaine Yeh, David Schnurr, Yung T Huang

  Journal of clinical microbiology. 09/2009;

  Enteroviruses (EVs) are common seasonal viruses that are associated with a variety of diseases. High quality monoclonal antibodies (MAbs) are needed to improve the accuracy of EV diagnosis inEnteroviruses (EVs) are common seasonal viruses that are associated with a variety of diseases. High quality monoclonal antibodies (MAbs) are needed to improve the accuracy of EV diagnosis in clinical laboratories. In the present study, the full-length VP1 genes of Poliovirus 1 (Polio 1) and Coxsackievirus B3 (Cox B3) were cloned and the encoded proteins were expressed and used as antigens in an attempt to raise broad spectrum MAbs to EVs. Two pan-EV MAbs were isolated, one raised against Polio 1 VP1 and the other against Cox B3 VP1. The binding sites of both pan-EV MAbs were mapped to an amino acid sequence within a conserved region in the N terminus of Polio 1 VP1 by peptide and competition ELISA. Two additional MAbs, an EV70-specific MAb and an EV71/Cox A16-bispecific MAb, developed against EV70 and 71 VP1 proteins were pooled with the two pan-EV MAbs (Pan-EV MAb Mix) and tested for their sensitivity and specificity in the staining of various virus-infected cells. The Pan-EV MAb Mix detected all 40 prototype EVs tested and showed no cross-reactivity to 18 different non-EV human viruses. When compared with two commercially available EV tests, the Pan-EV MAb Mix exhibited higher specificity than one and broader spectrum reactivity than the other. Thus, our study demonstrates that full-length Polio 1 VP1 and Cox B3 VP1 can serve as effective antigens for developing a pan-EV MAb and the Pan-EV MAb Mix can be used for the laboratory diagnosis of a wide range of EV infections.

• Identification of a novel human gamma-papillomavirus species.

  Authors: Linlin Li, Pennan Barry, Elaine Yeh, Carol Glaser, David Schnurr, Eric Delwart

  The Journal of general virology. 08/2009;

  Using random PCR amplification, shotgun sequencing and sequence similarity searches, we analyzed nucleic acids present in cell cultures inoculated with samples from unexplained cases of encephalitis.Using random PCR amplification, shotgun sequencing and sequence similarity searches, we analyzed nucleic acids present in cell cultures inoculated with samples from unexplained cases of encephalitis. We identified a divergent human papillomavirus sequence originating from a rectal swab. The full genome was amplified by inverse PCR and sequenced. The prototype of the sixth Gamma-papillomavirus species, HPV116 was not found in the patient's CSF or respiratory secretions nor in culture supernatants from other unexplained cases of encephalitis, indicating that its identification in an encephalitis patient was likely fortuitous.

• In vitro susceptibility to rhinovirus infection is greater for bronchial than for nasal airway epithelial cells in human subjects.

  Authors: Nilceia Lopez-Souza, Silvio Favoreto, Hofer Wong, Theresa Ward, Shigeo Yagi, David Schnurr, Walter E Finkbeiner, Gregory M Dolganov, Jonathan H Widdicombe, Homer A Boushey, Pedro C Avila

  The Journal of allergy and clinical immunology. 06/2009;

  BACKGROUND: Human rhinoviruses (HRVs) characteristically cause upper respiratory tract infection, but they also infect the lower airways, causing acute bronchitis and exacerbating asthma. OBJECTIVE:BACKGROUND: Human rhinoviruses (HRVs) characteristically cause upper respiratory tract infection, but they also infect the lower airways, causing acute bronchitis and exacerbating asthma. OBJECTIVE: Our purpose was to study ex vivo the differences in the response to HRV infection of nasal and bronchial epithelial cultures from the same healthy and asthmatic individuals using conditions favoring development of fully differentiated, pseudostratified mucociliary epithelium. METHODS: Cells from the inferior turbinates and bronchial tree of 5 healthy and 6 asthmatic individuals were cultured at an air-liquid interface. Cultures were infected with HRV-16, and after 48 hours, the degree of infection was measured. RESULTS: Baseline median transepithelial resistance was lower in human bronchial epithelial (HBE) cell cultures than in human nasal epithelial (HNE) cell cultures (195 Omega.cm(2) [95% CI, 164-252] vs 366 Omega.cm(2) [95% CI, 234-408], respectively; P < .01). Virus replicated more easily in HBE cells than in HNE cells based on virus shedding in apical wash (log tissue culture infective dose of 50%/0.1 mL = 2.0 [95% CI, 1.0-2.5] vs 0.5 [95% CI, 0.5-1.5], P < .01) and on a 20- to 30-fold greater viral load and number of infected cells in HBE cell cultures than in HNE cell cultures. The increases in expression of RANTES and double-stranded RNA-dependent protein kinase were greater in HBE cell cultures than in HNE cell cultures, as were the concentrations of IL-8, IL-1alpha, RANTES, and IP-10 in basolateral medium. However, no significant differences between asthmatic and healthy subjects (including IFN-beta1 expression) were found. CONCLUSIONS: Differentiated nasal epithelial cells might have mechanisms of increased resistance to rhinovirus infection compared with bronchial epithelial cells. We could not confirm previous reports of increased susceptibility to HRV infection in epithelial cells from asthmatic subjects.

• Evidence of molecular evolution driven by recombination events influencing tropism in a novel human adenovirus that causes epidemic keratoconjunctivitis.

  Authors: Michael P Walsh, Ashish Chintakuntlawar, Christopher M Robinson, Ijad Madisch, Balázs Harrach, Nolan R Hudson, David Schnurr, Albert Heim, James Chodosh, Donald Seto, Morris S Jones

  PloS one. 02/2009; 4(6):e5635.

  In 2005, a human adenovirus strain (formerly known as HAdV-D22/H8 but renamed here HAdV-D53) was isolated from an outbreak of epidemic keratoconjunctititis (EKC), a disease that is usually caused byIn 2005, a human adenovirus strain (formerly known as HAdV-D22/H8 but renamed here HAdV-D53) was isolated from an outbreak of epidemic keratoconjunctititis (EKC), a disease that is usually caused by HAdV-D8, -D19, or -D37, not HAdV-D22. To date, a complete change of tropism compared to the prototype has never been observed, although apparent recombinant strains of other viruses from species Human adenovirus D (HAdV-D) have been described. The complete genome of HAdV-D53 was sequenced to elucidate recombination events that lead to the emergence of a viable and highly virulent virus with a modified tropism. Bioinformatic and phylogenetic analyses of this genome demonstrate that this adenovirus is a recombinant of HAdV-D8 (including the fiber gene encoding the primary cellular receptor binding site), HAdV-D22, (the epsilon determinant of the hexon gene), HAdV-D37 (including the penton base gene encoding the secondary cellular receptor binding site), and at least one unknown or unsequenced HAdV-D strain. Bootscanning analysis of the complete genomic sequence of this novel adenovirus, which we have re-named HAdV-D53, indicated at least five recombination events between the aforementioned adenoviruses. Intrahexon recombination sites perfectly framed the epsilon neutralization determinant that was almost identical to the HAdV-D22 prototype. Additional bootscan analysis of all HAdV-D hexon genes revealed recombinations in identical locations in several other adenoviruses. In addition, HAdV-D53 but not HAdV-D22 induced corneal inflammation in a mouse model. Serological analysis confirmed previous results and demonstrated that HAdV-D53 has a neutralization profile representative of the epsilon determinant of its hexon (HAdV-D22) and the fiber (HAdV-D8) proteins. Our recombinant hexon sequence is almost identical to the hexon sequences of the HAdV-D strain causing EKC outbreaks in Japan, suggesting that HAdV-D53 is pandemic as an emerging EKC agent. This documents the first genomic, bioinformatic, and biological descriptions of the molecular evolution events engendering an emerging pathogenic adenovirus.

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• Enterovirus-associated encephalitis in the california encephalitis project, 1998-2005.

  Authors: Ashley L Fowlkes, Somayeh Honarmand, Carol Glaser, Shigeo Yagi, David Schnurr, M Steven Oberste, Larry Anderson, Mark A Pallansch, Nino Khetsuriani

  The Journal of infectious diseases. 01/2009; 198(11):1685-91.

  Background. @nbsp; Encephalitis is a relatively rare presentation of enterovirus (EV) infections. Clinical and epidemiologic characteristics of EV encephalitis (EVE) have not been well characterized.Background. @nbsp; Encephalitis is a relatively rare presentation of enterovirus (EV) infections. Clinical and epidemiologic characteristics of EV encephalitis (EVE) have not been well characterized. Methods. @nbsp; Patients with encephalitis enrolled in the California Encephalitis Project from 1998 to 2005 were tested for a range of pathogens, including EV, using a standardized diagnostic algorithm. EVE was categorized as "confirmed" (EV detected in cerebrospinal fluid [CSF] or brain tissue) or "possible" (EV found in respiratory or fecal specimens or serum EV immunoglobulin [Ig] M detected). We compared clinical and epidemiologic characteristics of EVE with those of other infectious encephalitis cases. Results. @nbsp; EVE was diagnosed in 73 (4.6%) of 1571 patients (45 confirmed cases, 28 possible cases); 11.1% of cases had other infectious causes. Patients with confirmed EVE were younger, although 27% were adults, who presented with significantly less severe symptoms. Serotypes identified in EVE cases correlated with the predominant serotype for the given year reported to the National Enterovirus Surveillance System at the Centers for Disease Control and Prevention. Two of 4 fatal EVE cases were associated with EV71. Conclusion. @nbsp; EVs are an important cause of encephalitis cases requiring hospitalization, in both children and adults. Our data suggest that EVE severity varies by serotype, confirm the importance of CSF/brain tissue polymerase chain reaction, and demonstrate that serum IgM findings are of little value in diagnosing EVE.

• Utility of DNA microarrays for detection of viruses in acute respiratory tract infections in children.

  Authors: Charles Y Chiu, Anatoly Urisman, Tara L Greenhow, Silvi Rouskin, Shigeo Yagi, David Schnurr, Carolyn Wright, W Lawrence Drew, David Wang, Peggy S Weintrub, Joseph L DeRisi, Don Ganem

  The Journal of pediatrics. 08/2008; 153(1):76-83.

  OBJECTIVE: To assess the utility of a panviral DNA microarray platform (Virochip) in the detection of viruses associated with pediatric respiratory tract infections (RTIs). STUDY DESIGN: The VirochipOBJECTIVE: To assess the utility of a panviral DNA microarray platform (Virochip) in the detection of viruses associated with pediatric respiratory tract infections (RTIs). STUDY DESIGN: The Virochip was compared with conventional direct fluorescent antibody (DFA)- and polymerase chain reaction (PCR)-based testing for the detection of respiratory viruses in 278 consecutive nasopharyngeal aspirate samples from 222 children. RESULTS: The Virochip was superior in performance to DFA, showing a 19% increase in the detection of 7 respiratory viruses included in standard DFA panels, and was similar to virus-specific PCR (sensitivity, 85% to 90%; specificity, >/=99%; positive predictive value, 94% to 96%; negative predictive value, 97% to 98%) in the detection of respiratory syncytial virus, influenza A, and rhinoviruses/enteroviruses. The Virochip also detected viruses not routinely tested for or missed by DFA and PCR, as well as double infections and infections in critically ill patients that DFA failed to detect. CONCLUSIONS: Given its favorable sensitivity and specificity profile and expanded spectrum for detection, microarray-based viral testing holds promise for clinical diagnosis of pediatric RTIs.

• Molecular identification of 13 new enterovirus types, EV79-88, EV97, and EV100-101, members of the species Human Enterovirus B.

  Authors: M Steven Oberste, Kaija Maher, William A Nix, Suzanne M Michele, Moyez Uddin, David Schnurr, Suleiman al-Busaidy, Chantal Akoua-Koffi, Mark A Pallansch

  Virus research. 10/2007; 128(1-2):34-42.

  Molecular methods have enabled the rapid identification of new enterovirus (EV) serotypes that are untypeable using existing neutralizing antisera. As a result, sequencing of the VP1 capsid gene hasMolecular methods have enabled the rapid identification of new enterovirus (EV) serotypes that are untypeable using existing neutralizing antisera. As a result, sequencing of the VP1 capsid gene has been developed as a surrogate for antigenic typing to distinguish enterovirus types. In this study, 17 enterovirus isolates from four countries were identified as members of 13 new types within the species Human Enterovirus B (HEV-B) by complete genome sequencing. Members of each of these new types are at least 75% identical to one another (91% amino acid identity) in VP1, but members of different types differ from one another and from other enteroviruses by at least 27% in nucleotide sequence (26% amino acid sequence difference). The complete P1 (capsid) sequences of the new types are at least 17% different from those of all other enterovirus serotypes (14.5% amino acid sequence difference), but they are highly conserved within a type (<8% amino acid sequence difference). For both VP1 and P1, the 17 isolates are monophyletic by type with respect to all other EV serotypes. The P2 and P3 sequences are closely related to those of other HEV-B viruses (>93% amino acid identity), confirming that the 17 new strains belong to HEV-B. We propose that these 17 isolates be classified as members of 13 new human enterovirus types, enteroviruses 79-88, 97, and 100-101.

• Pan-viral screening of respiratory tract infections in adults with and without asthma reveals unexpected human coronavirus and human rhinovirus diversity.

  Authors: Amy Kistler, Pedro C Avila, Silvi Rouskin, David Wang, Theresa Ward, Shigeo Yagi, David Schnurr, Don Ganem, Joseph L DeRisi, Homer A Boushey

  The Journal of infectious diseases. 09/2007; 196(6):817-25.

  BACKGROUND: Between 50% and 80% of asthma exacerbations are associated with viral respiratory tract infections (RTIs), yet the influence of viral pathogen diversity on asthma outcomes is poorlyBACKGROUND: Between 50% and 80% of asthma exacerbations are associated with viral respiratory tract infections (RTIs), yet the influence of viral pathogen diversity on asthma outcomes is poorly understood because of the limited scope and throughput of conventional viral detection methods. METHODS: We investigated the capability of the Virochip, a DNA microarray-based viral detection platform, to characterize viral diversity in RTIs in adults with and without asthma. RESULTS: The Virochip detected viruses in a higher proportion of samples (65%) than did culture isolation (17%) while exhibiting high concordance (98%) with and comparable sensitivity (97%) and specificity (98%) to pathogen-specific polymerase chain reaction. A similar spectrum of viruses was identified in the RTIs of each patient subgroup; however, unexpected diversity among human coronaviruses (HCoVs) and human rhinoviruses (HRVs) was revealed. All but one of the HCoVs corresponded to the newly recognized HCoV-NL63 and HCoV-HKU1 viruses, and >20 different serotypes of HRVs were detected, including a set of 5 divergent isolates that formed a distinct genetic subgroup. CONCLUSIONS: The Virochip can detect both known and novel variants of viral pathogens present in RTIs. Given the diversity detected here, larger-scale studies will be necessary to determine whether particular substrains of viruses confer an elevated risk of asthma exacerbation.

• Diagnosis of a critical respiratory illness caused by human metapneumovirus by use of a pan-virus microarray.

  Authors: Charles Y Chiu, Ash A Alizadeh, Silvi Rouskin, Jason D Merker, Elaine Yeh, Shigeo Yagi, David Schnurr, Bruce K Patterson, Don Ganem, Joseph L DeRisi

  Journal of clinical microbiology. 08/2007; 45(7):2340-3.

  A pan-virus DNA microarray (Virochip) was used to detect a human metapneumovirus (hMPV) strain associated with a critical respiratory tract infection in an elderly adult with chronic lymphocyticA pan-virus DNA microarray (Virochip) was used to detect a human metapneumovirus (hMPV) strain associated with a critical respiratory tract infection in an elderly adult with chronic lymphocytic leukemia. This infection had previously eluded diagnosis despite extensive microbiological testing for possible etiologic agents. The patient's hMPV strain did not grow in viral culture, and only one of five specific reverse transcription-PCR assays for hMPV was positive.

• Genome-wide diversity and selective pressure in the human rhinovirus

  Authors: Amy Kistler, Dale Webster, Silvi Rouskin, Vince Magrini, Joel Credle, David Schnurr, Homer Boushey, Elaine Mardis, Hao Li, Joseph DeRisi

  Virology Journal. 01/2007;

  Abstract Background The human rhinoviruses (HRV) are one of the most common and diverse respiratory pathogens of humans. Over 100 distinct HRV serotypes are known, yet only 6 genomes are available.Abstract Background The human rhinoviruses (HRV) are one of the most common and diverse respiratory pathogens of humans. Over 100 distinct HRV serotypes are known, yet only 6 genomes are available. Due to the paucity of HRV genome sequence, little is known about the genetic diversity within HRV or the forces driving this diversity. Previous comparative genome sequence analyses indicate that recombination drives diversification in multiple genera of the picornavirus family, yet it remains unclear if this holds for HRV. Results To resolve this and gain insight into the forces driving diversification in HRV, we generated a representative set of 34 fully sequenced HRVs. Analysis of these genomes shows consistent phylogenies across the genome, conserved non-coding elements, and only limited recombination. However, spikes of genetic diversity at both the nucleotide and amino acid level are detectable within every locus of the genome. Despite this, the HRV genome as a whole is under purifying selective pressure, with islands of diversifying pressure in the VP1, VP2, and VP3 structural genes and two non-structural genes, the 3C protease and 3D polymerase. Mapping diversifying residues in these factors onto available 3-dimensional structures revealed the diversifying capsid residues partition to the external surface of the viral particle in statistically significant proximity to antigenic sites. Diversifying pressure in the pleconaril binding site is confined to a single residue known to confer drug resistance (VP1 191). In contrast, diversifying pressure in the non-structural genes is less clear, mapping both nearby and beyond characterized functional domains of these factors. Conclusion This work provides a foundation for understanding HRV genetic diversity and insight into the underlying biology driving evolution in HRV. It expands our knowledge of the genome sequence space that HRV reference serotypes occupy and how the pattern of genetic diversity across HRV genomes differs from other picornaviruses. It also reveals evidence of diversifying selective pressure in both structural genes known to interact with the host immune system and in domains of unassigned function in the non-structural 3C and 3D genes, raising the possibility that diversification of undiscovered functions in these essential factors may influence HRV fitness and evolution.

• Genetic analysis of rubella viruses found in the United States between 1966 and 2004: evidence that indigenous rubella viruses have been eliminated.

  Authors: Joseph P Icenogle, Teryl K Frey, Emily Abernathy, Susan E Reef, David Schnurr, John A Stewart

  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 12/2006; 43 Suppl 3:S133-40.

  Wild-type rubella viruses are genetically classified into 2 clades and 10 intraclade genotypes, of which 3 are provisional. The genotypes of 118 viruses from the United States were determined byWild-type rubella viruses are genetically classified into 2 clades and 10 intraclade genotypes, of which 3 are provisional. The genotypes of 118 viruses from the United States were determined by sequencing part of the E1 coding region of these viruses and comparing the resulting sequences with reference sequences for each genotype, using the Bayesian inference program MRBAYES. Three genotypes of rubella viruses were found in the United States too infrequently to be considered for indigenous transmission. A fourth genotype was found frequently until 1981, and a fifth genotype was found frequently until 1988, but neither was obtained from nonimported cases after 1988. A sixth genotype was found frequently during 1996-2000, likely because of multiple importations from neighboring countries. The results of the present genetic analysis of rubella viruses found in the United States are consistent with elimination of indigenous viruses by 2001, the year when rubella was considered to be eliminated on the basis of epidemiological evidence.

• Microarray detection of human parainfluenzavirus 4 infection associated with respiratory failure in an immunocompetent adult.

  Authors: Charles Y Chiu, Silvi Rouskin, Anita Koshy, Anatoly Urisman, Kael Fischer, Shigeo Yagi, David Schnurr, Paul B Eckburg, Lucy S Tompkins, Brian G Blackburn, Jason D Merker, Bruce K Patterson, Don Ganem, Joseph L DeRisi

  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 11/2006; 43(8):e71-6.

  A pan-viral DNA microarray, the Virochip (University of California, San Francisco), was used to detect human parainfluenzavirus 4 (HPIV-4) infection in an immunocompetent adult presenting with aA pan-viral DNA microarray, the Virochip (University of California, San Francisco), was used to detect human parainfluenzavirus 4 (HPIV-4) infection in an immunocompetent adult presenting with a life-threatening acute respiratory illness. The virus was identified in an endotracheal aspirate specimen, and the microarray results were confirmed by specific polymerase chain reaction and serological analysis for HPIV-4. Conventional clinical laboratory testing using an extensive panel of microbiological tests failed to yield a diagnosis. This case suggests that the potential severity of disease caused by HPIV-4 in adults may be greater than previously appreciated and illustrates the clinical utility of a microarray for broad-based viral pathogen screening.

• Rhinovirus induces airway epithelial gene expression through double-stranded RNA and IFN-dependent pathways.

  Authors: Yin Chen, Edward Hamati, Pak-Kei Lee, Wai-Ming Lee, Shinichiro Wachi, David Schnurr, Shigeo Yagi, Gregory Dolganov, Homer Boushey, Pedro Avila, Reen Wu

  American journal of respiratory cell and molecular biology. 03/2006; 34(2):192-203.

  Rhinovirus (RV) infection is the major cause of common colds and of asthma exacerbations. Because the epithelial cell layer is the primary target of RV infection, we hypothesize that RV-inducedRhinovirus (RV) infection is the major cause of common colds and of asthma exacerbations. Because the epithelial cell layer is the primary target of RV infection, we hypothesize that RV-induced airway disease is associated with the perturbation of airway epithelial gene expression. In this study, well differentiated primary human airway epithelial cells were infected with either RV16 (major group) or RV1B (minor group). Transcriptional gene profiles from RV-infected and mock-infected control cells were analyzed by Affymetrix Genechip, and changes of the gene expression were confirmed by real-time RT-PCR analysis. At 24 h after infection, 48 genes induced by both viruses were identified. Most of these genes are related to the IFN pathway, and have been documented to have antiviral functions. Indeed, a significant stimulation of IFN-beta secretion was detected after RV16 infection. Neutralizing antibody specific to IFN-beta and a specific inhibitor of the Janus kinase pathway both significantly blocked the induction of RV-inducible genes. Further studies demonstrated that 2-aminopurine, a specific inhibitor double-stranded RNA-dependent protein kinase, could block both IFN-beta production and RV-induced gene expression. Thus, IFN-beta-dependent pathway is a part of the double-stranded RNA-initiated pathway that is responsible for RV-induced gene expression. Consistent with its indispensable role in the induction of antiviral genes, deactivation of this signaling pathway significantly enhanced viral production. Because increase of viral yield is associated with the severity of RV-induced airway illness, the discovery of an epithelial antiviral signaling pathway in this study will contribute to our understanding of the pathogenesis of RV-induced colds and asthma exacerbations.

• Myocarditis Outbreak among Adults, Illinois, 2003.

  Authors: Gregory D Huhn, Cindy Gross, David Schnurr, Chris Preas, Shigeo Yagi, Sarah Reagan, Chris Paddock, Douglas Passaro, Mark S Dworkin

  Emerging infectious diseases. 11/2005; 11(10):1621-4.

  An outbreak of myocarditis occurred among adults in Illinois in 2003. Diagnostic testing of myocardial tissues from 3 patients and comprehensive tests for enterovirus and adenovirus of otherAn outbreak of myocarditis occurred among adults in Illinois in 2003. Diagnostic testing of myocardial tissues from 3 patients and comprehensive tests for enterovirus and adenovirus of other specimens from patients were inconclusive. Appropriate specimen collection from patients with idiopathic cardiomyopathy and further enhancement of diagnostic techniques are needed.

• Clinical, epidemiologic, and environmental surveillance for ehrlichiosis and anaplasmosis in an endemic area of northern California.

  Authors: Curtis L Fritz, Lawrence R Bronson, Charles R Smith, Leta Crawford-Miksza, Elaine Yeh, David Schnurr

  Journal of vector ecology : journal of the Society for Vector Ecology. 07/2005; 30(1):4-10.

  Two forms of tick-borne leukocytotropic rickettsioses have been recognized in California since the mid-1990s: human monocytic ehrlichiosis (HME) caused by Ehrlichia chaffeensis and human granulocyticTwo forms of tick-borne leukocytotropic rickettsioses have been recognized in California since the mid-1990s: human monocytic ehrlichiosis (HME) caused by Ehrlichia chaffeensis and human granulocytic anaplasmosis (HGA) caused by Anaplasma phagocytophilum. Between 1997 and 1999, two cases of HME and four cases of HGA were diagnosed in residents of southern Humboldt County, California. Environmental followup at case-patients' residences revealed dense populations of Ixodes pacificus ticks, particularly in grassy roadside areas. PCR evidence of A. phagocytophilum was detected in approximately 2.0% of I. pacificus; E. chaffeensis was not detected in any of 625 ticks tested. Serologic antibody to A. phagocytophilum was detected in two of 54 participants in a community epidemiologic study; one of these also had antibody to E. chaffeensis. Over 85% of study participants reported finding a tick on themselves in the preceding 12 mo. Residents of southern Humboldt County are at significant risk of tick bites and should take appropriate prevention measures to avoid infection with rickettsia and other tick-transmitted pathogens.