Larry J Anderson

Publications of Larry J Anderson

• Genomic characterization of seven distinct bat coronaviruses in Kenya.

  Authors: Ying Tao, Kevin Tang, Mang Shi, Christina Conrardy, Kenneth S M Li, Susanna K P Lau, Larry J Anderson, Suxiang Tong

  Virus research. 04/2012;

  To better understand the genetic diversity and genomic features of 41 coronaviruses (CoVs) identified from Kenya bats in 2006, seven CoVs as representatives of seven different phylogenetic groupsTo better understand the genetic diversity and genomic features of 41 coronaviruses (CoVs) identified from Kenya bats in 2006, seven CoVs as representatives of seven different phylogenetic groups identified from partial polymerase gene sequences, were subjected to extensive genomic sequencing. As a result, 15-16kb nucleotide sequences encoding complete RNA dependent RNA polymerase, spike, envelope, membrane, and nucleocapsid proteins plus other open reading frames (ORFs) were generated. Sequences analysis confirmed that the CoVs from Kenya bats are divergent members of Alphacoronavirus and Betacoronavirus genera. Furthermore, the CoVs BtKY22, BtKY41, and BtKY43 in Alphacoronavirus genus and BtKY24 in Betacoronavirus genus are likely representatives of 4 novel CoV species. BtKY27 and BtKY33 are members of the established bat CoV species in Alphacoronavirus genus and BtKY06 is a member of the established bat CoV species in Betacoronavirus genus. The genome organization of these seven CoVs is similar to other known CoVs from the same groups except for differences in the number of putative ORFs following the N gene. The present results confirm a significant diversity of CoVs circulating in Kenya bats. These Kenya bat CoVs are phylogenetically distant from any previously described human and animal CoVs. However, because of the examples of host switching among CoVs after relatively minor sequence changes in S1 domain of spike protein, a further surveillance in animal reservoirs and understanding the interface between host susceptibility is critical for predicting and preventing the potential threat of bat CoVs to public health.

• Hospitalizations Associated With Influenza and Respiratory Syncytial Virus in the United States, 1993-2008.

  Authors: Hong Zhou, William W Thompson, Cecile G Viboud, Corinne M Ringholz, Po-Yung Cheng, Claudia Steiner, Glen R Abedi, Larry J Anderson, Lynnette Brammer, David K Shay

  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 04/2012;

  Background. Age-specific comparisons of influenza and respiratory syncytial virus (RSV) hospitalization rates can inform prevention efforts, including vaccine development plans. Previous US studiesBackground. Age-specific comparisons of influenza and respiratory syncytial virus (RSV) hospitalization rates can inform prevention efforts, including vaccine development plans. Previous US studies have not estimated jointly the burden of these viruses using similar data sources and over many seasons.Methods. We estimated influenza and RSV hospitalizations in 5 age categories (<1, 1-4, 5-49, 50-64, and ≥65 years) with data for 13 states from 1993-1994 through 2007-2008. For each state and age group, we estimated the contribution of influenza and RSV to hospitalizations for respiratory and circulatory disease by using negative binomial regression models that incorporated weekly influenza and RSV surveillance data as covariates.Results. Mean rates of influenza and RSV hospitalizations were 63.5 (95% confidence interval [CI], 37.5-237) and 55.3 (95% CI, 44.4-107) per 100000 person-years, respectively. The highest hospitalization rates for influenza were among persons aged ≥65 years (309/100000; 95% CI, 186-1100) and those aged <1 year (151/100000; 95% CI, 151-660). For RSV, children aged <1 year had the highest hospitalization rate (2350/100000; 95% CI, 2220-2520) followed by those aged 1-4 years (178/100000; 95% CI, 155-230). Age-standardized annual rates per 100000 person-years varied substantially for influenza (33-100) but less for RSV (42-77).Conclusions. Overall US hospitalization rates for influenza and RSV are similar; however, their age-specific burdens differ dramatically. Our estimates are consistent with those from previous studies focusing either on influenza or RSV. Our approach provides robust national comparisons of hospitalizations associated with these 2 viral respiratory pathogens by age group and over time.

• A distinct lineage of influenza A virus from bats.

  Authors: Suxiang Tong, Yan Li, Pierre Rivailler, Christina Conrardy, Danilo A Alvarez Castillo, Li-Mei Chen, Sergio Recuenco, James A Ellison, Charles T Davis, Ian A York [......] Kevin Tang, Lori A Rowe, Scott Sammons, Xiyan Xu, Michael Frace, Kim A Lindblade, Nancy J Cox, Larry J Anderson, Charles E Rupprecht, Ruben O Donis

  Proceedings of the National Academy of Sciences of the United States of America. 02/2012; 109(11):4269-74.

  Influenza A virus reservoirs in animals have provided novel genetic elements leading to the emergence of global pandemics in humans. Most influenza A viruses circulate in waterfowl, but those thatInfluenza A virus reservoirs in animals have provided novel genetic elements leading to the emergence of global pandemics in humans. Most influenza A viruses circulate in waterfowl, but those that infect mammalian hosts are thought to pose the greatest risk for zoonotic spread to humans and the generation of pandemic or panzootic viruses. We have identified an influenza A virus from little yellow-shouldered bats captured at two locations in Guatemala. It is significantly divergent from known influenza A viruses. The HA of the bat virus was estimated to have diverged at roughly the same time as the known subtypes of HA and was designated as H17. The neuraminidase (NA) gene is highly divergent from all known influenza NAs, and the internal genes from the bat virus diverged from those of known influenza A viruses before the estimated divergence of the known influenza A internal gene lineages. Attempts to propagate this virus in cell cultures and chicken embryos were unsuccessful, suggesting distinct requirements compared with known influenza viruses. Despite its divergence from known influenza A viruses, the bat virus is compatible for genetic exchange with human influenza viruses in human cells, suggesting the potential capability for reassortment and contributions to new pandemic or panzootic influenza A viruses.

• Human rhinovirus species associated with hospitalizations for acute respiratory illness in young US children.

  Authors: Marika K Iwane, Mila M Prill, Xiaoyan Lu, E Kathryn Miller, Kathryn M Edwards, Caroline B Hall, Marie R Griffin, Mary A Staat, Larry J Anderson, John V Williams, Geoffrey A Weinberg, Asad Ali, Peter G Szilagyi, Yuwei Zhu, Dean D Erdman

  The Journal of infectious diseases. 12/2011; 204(11):1702-10.

  The contribution of human rhinovirus (HRV) to severe acute respiratory illness (ARI) is unclear. To assess the association between HRV species detection and ARI hospitalizations. Children <5 yearsThe contribution of human rhinovirus (HRV) to severe acute respiratory illness (ARI) is unclear. To assess the association between HRV species detection and ARI hospitalizations. Children <5 years old hospitalized for ARI were prospectively enrolled between December 2003 and April 2005 in 3 US counties. Asymptomatic controls were enrolled between December 2003 and March 2004 and between October 2004 and April 2005 in clinics. Nasal and throat swab samples were tested for HRV and other viruses (ie, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, and influenza virus) by reverse-transcription-polymerase chain reaction, and genetic sequencing identified HRV species and types. HRV species detection was compared between controls and patients hospitalized during months in which controls were enrolled. A total of 1867 children with 1947 ARI hospitalizations and 784 controls with 790 clinic visits were enrolled and tested for HRV. The HRV-A detection rate among participants ≥24 months old was 8.1% in the hospitalized group and 2.2% in the control group (P = .009), and the HRV-C detection rates among those ≥6 months old were 8.2% and 3.9%, respectively (P = .002); among younger children, the detection rates for both species were similar between groups. The HRV-B detection rate was ≤1%. A broad diversity of HRV types was observed in both groups. Clinical presentations were similar among HRV species. Compared with children infected with other viruses, children with HRV detected were similar for severe hospital outcomes and more commonly had histories or diagnoses of asthma or wheezing. HRV-A and HRV-C were associated with ARI hospitalization and serious illness outcomes.

• Development of a recombinant truncated nucleocapsid protein based immunoassay for detection of antibodies against human coronavirus OC43.

  Authors: Elisabeth G Blanchard, Congrong Miao, Thomas E Haupt, Larry J Anderson, Lia M Haynes

  Journal of virological methods. 10/2011; 177(1):100-6.

  Human coronaviruses are one of the main causes of upper respiratory tract infections in humans. While more often responsible for mild illness, they have been associated with illnesses that requireHuman coronaviruses are one of the main causes of upper respiratory tract infections in humans. While more often responsible for mild illness, they have been associated with illnesses that require hospitalization. In this study, an assay for one of the human coronaviruses, OC43, was developed using a truncated recombinant nucleocapsid (N) protein antigen in an enzyme immunosorbent assay (ELISA) and evaluated using serum collected from HCoV-OC43-infected patients, healthy adults, and patients with other respiratory virus infections. Results showed that the diagnostic sensitivity and specificity of the assay were 90.9% (10/11) and 82.9% (39/47), respectively. To evaluate the clinical utility of the ELISA, serum samples collected from patients during an outbreak of HCoV-OC43 infection and previously identified as positive by HCoV-OC43 whole N ELISA were screened resulting in 100% diagnosis agreement between the testing methods. These results suggest that this assay offers a reliable method to detect HCoV-OC43 infection and may be a useful tool in coronavirus seroepidemiological studies.

• Respiratory syncytial virus-associated hospitalizations among infants and young children in the United States, 1997-2006.

  Authors: Lauren J Stockman, Aaron T Curns, Larry J Anderson, Gayle Fischer-Langley

  The Pediatric infectious disease journal. 08/2011; 31(1):5-9.

  Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease among young children in the United States. RSV-associated hospitalization increased among children in theRespiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease among young children in the United States. RSV-associated hospitalization increased among children in the United States during 1980 through 1996. In this study, we updated national estimates of RSV hospitalization rates among US children through 2006. We conducted a retrospective analysis of hospital discharges for lower respiratory tract illness (LRTI) in children <5 years old from the National Hospital Discharge Survey. LRTI hospitalizations were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification codes. RSV-coded hospitalizations were International Classification of Diseases, Ninth Revision, Clinical Modification codes 466.11, 480.1, and 079.6. RSV-associated hospitalizations were the sum of RSV-coded hospitalizations and a proportion of hospitalizations coded as bronchiolitis and pneumonia during the RSV season. RSV-coded hospitalizations accounted for 24% of an estimated 5.5 million LRTI hospitalizations among children <5 years of age during the 10 study years, 1997-2006. The RSV-coded hospitalization rate in infants <1 year old was 26.0 per 1000, with no significant difference between study years. The hospitalization rate was highest among infants <3 months old (48.9 per 1000), followed by infants 3 to 5 months old (28.4 per 1000), and lower among those >1 year old (1.8 per 1000). An estimated 132,000 to 172,000 RSV-associated hospitalizations occurred annually in children <5 years of age. RSV hospitalization rates remained steady during 1997 to 2006 and were a substantial burden in the United States, especially among infants and young children. A safe and effective RSV vaccine is needed.

• Epidemiology and prevention of respiratory syncytial virus infections among infants and young children.

  Authors: Gayle Fischer Langley, Larry J Anderson

  The Pediatric infectious disease journal. 06/2011; 30(6):510-7.

  Since its discovery in 1956, respiratory syncytial virus (RSV) has been recognized as one of the most common causes of serious lower respiratory tract infections in young children worldwide. WhileSince its discovery in 1956, respiratory syncytial virus (RSV) has been recognized as one of the most common causes of serious lower respiratory tract infections in young children worldwide. While considered a high priority, development of a safe and effective vaccine has remained elusive. Prevention of RSV disease relies on infection control and hygiene measures, as well as providing immunoprophylaxis in select infants. The prophylaxis, however, is costly, and so targeting the recipient population and timing of administration is important for optimal effectiveness and judicious use of limited health care resources. This article reviews the epidemiology of RSV infections in infants and young children, including risk factors for severe disease, so as to inform decisions about prevention efforts.

• Application of TaqMan low-density arrays for simultaneous detection of multiple respiratory pathogens.

  Authors: Maja Kodani, Genyan Yang, Laura M Conklin, Tatiana C Travis, Cynthia G Whitney, Larry J Anderson, Stephanie J Schrag, Thomas H Taylor, Bernard W Beall, Robert F Breiman, Daniel R Feikin, M Kariuki Njenga, Leonard W Mayer, M Steven Oberste, Maria Lucia C Tondella, Jonas M Winchell, Stephen L Lindstrom, Dean D Erdman, Barry S Fields

  Journal of clinical microbiology. 04/2011; 49(6):2175-82.

  The large and growing number of viral and bacterial pathogens responsible for respiratory infections poses a challenge for laboratories seeking to provide rapid and comprehensive pathogenThe large and growing number of viral and bacterial pathogens responsible for respiratory infections poses a challenge for laboratories seeking to provide rapid and comprehensive pathogen identification. We evaluated a novel application of the TaqMan low-density array (TLDA) cards for real-time PCR detection of 21 respiratory-pathogen targets. The performance of the TLDA was compared to that of individual real-time PCR (IRTP) assays with the same primers and probes using (i) nucleic acids extracted from the 21 pathogen strains and 66 closely related viruses and bacteria and (ii) 292 clinical respiratory specimens. With spiked samples, TLDA cards were about 10-fold less sensitive than IRTP assays. By using 292 clinical specimens to generate 2,238 paired individual assays, the TLDA card exhibited 89% sensitivity (95% confidence interval [CI], 86 to 92%; range per target, 47 to 100%) and 98% specificity (95% CI, 97 to 99%; range per target, 85 to 100%) overall compared to IRTP assays as the gold standard with a threshold cycle (C(T)) cutoff of 43. The TLDA card approach offers promise for rapid and simultaneous identification of multiple respiratory pathogens for outbreak investigations and disease surveillance.

• Evaluation of the Calu-3 cell line as a model of in vitro respiratory syncytial virus infection.

  Authors: Jennifer L Harcourt, Hayat Caidi, Larry J Anderson, Lia M Haynes

  Journal of virological methods. 03/2011; 174(1-2):144-9.

  Respiratory syncytial virus (RSV) replication is primarily limited to the upper respiratory tract epithelium and primary, differentiated normal human bronchial epithelial cells (NHBE) have,Respiratory syncytial virus (RSV) replication is primarily limited to the upper respiratory tract epithelium and primary, differentiated normal human bronchial epithelial cells (NHBE) have, therefore, been considered a good system for in vitro analysis of lung tissue response to respiratory virus infection and virus-host interactions. However, NHBE cells are expensive, difficult to culture, and vary with the source patient. An alternate approach is to use a continuous cell line that has features of bronchial epithelial cells such as Calu-3, an epithelial cell line derived from human lung adenocarcinoma, as an in vitro model of respiratory virus infection. The results show that Calu-3 fully polarize when grown on permeable supports as liquid-covered cultures. Polarized Calu-3 are susceptible to RSV infection and release infectious virus primarily from the apical surface, consistent with studies in NHBE cells. The data demonstrate that polarized Calu-3 may serve as a useful in vitro model to study host responses to RSV infection.

• Respiratory syncytial virus and Staphylococcus aureus coinfection in children hospitalized with pneumonia.

  Authors: Lauren J Stockman, Carrie Reed, Alexander J Kallen, Lyn Finelli, Larry J Anderson

  The Pediatric infectious disease journal. 11/2010; 29(11):1048-50.

  Respiratory syncytial virus (RSV) infection might facilitate bacterial infection. We describe 5 patients with RSV among 30 children admitted to pediatric hospitals in Atlanta between October 1, 2006Respiratory syncytial virus (RSV) infection might facilitate bacterial infection. We describe 5 patients with RSV among 30 children admitted to pediatric hospitals in Atlanta between October 1, 2006 and April 30, 2007 with community-onset Staphylococcus aureus pneumonia. RSV-S. aureus patients were younger and had less medical comorbidity than those without RSV.

• Update on SARS research and other possibly zoonotic coronaviruses.

  Authors: Larry J Anderson, Suxiang Tong

  International journal of antimicrobial agents. 11/2010; 36 Suppl 1:S21-5.

  The global outbreak of severe acute respiratory syndrome (SARS) in 2003 led to an intense and effective global response that stopped the spread of the disease by July 2003. There was also anThe global outbreak of severe acute respiratory syndrome (SARS) in 2003 led to an intense and effective global response that stopped the spread of the disease by July 2003. There was also an intensive and very productive research effort to identify the aetiological agent, characterise the clinical and epidemiological features of the disease, understand the pathogenesis of the disease and the molecular biology of the virus, and design antiviral drugs and vaccines to treat and prevent the disease. In parallel with the SARS research effort there have been continuous improvements in our ability to detect and characterise other novel viruses. The SARS outbreak illustrates the importance of such detection tools in the response to public health threats. Studies since the SARS outbreak suggest that many novel viruses exist in animals and some, but probably not many, will present a risk to humans.

• Prophylactic treatment with a G glycoprotein monoclonal antibody reduces pulmonary inflammation in respiratory syncytial virus (RSV)-challenged naive and formalin-inactivated RSV-immunized BALB/c mice.

  Authors: Gertrud U Radu, Hayat Caidi, Congrong Miao, Ralph A Tripp, Larry J Anderson, Lia M Haynes

  Journal of virology. 09/2010; 84(18):9632-6.

  We examined whether prophylactically administered anti-respiratory syncytial virus (anti-RSV) G monoclonal antibody (MAb) would decrease the pulmonary inflammation associated with primary RSVWe examined whether prophylactically administered anti-respiratory syncytial virus (anti-RSV) G monoclonal antibody (MAb) would decrease the pulmonary inflammation associated with primary RSV infection and formalin-inactivated RSV (FI-RSV)-enhanced disease in mice. MAb 131-2G administration 1 day prior to primary infection reduced the pulmonary inflammatory response and the level of RSV replication. Further, intact or F(ab')(2) forms of MAb 131-2G administered 1 day prior to infection in FI-RSV-vaccinated mice reduced enhanced inflammation and disease. This study shows that an anti-RSV G protein MAb might provide prophylaxis against both primary infection and FI-RSV-associated enhanced disease. It is possible that antibodies with similar reactivities might prevent enhanced disease and improve the safety of nonlive virus vaccines.

• Outbreak of pneumonia associated with emergent human adenovirus serotype 14--Southeast Alaska, 2008.

  Authors: Douglas H Esposito, Tracie J Gardner, Eileen Schneider, Lauren J Stockman, Jacqueline E Tate, Catherine A Panozzo, Cheryl L Robbins, Sue A Jenkerson, Lorita Thomas, Colleen M Watson [......] Dean D Erdman, Xiaoyan Lu, Theresa Cromeans, Mary Westcott, Catherine Humphries, Jayme Ballantyne, Gayle E Fischer, Joseph B McLaughlin, Gregory Armstrong, Larry J Anderson

  The Journal of infectious diseases. 07/2010; 202(2):214-22.

  In September 2008, an outbreak of pneumonia associated with an emerging human adenovirus (human adenovirus serotype 14 [HAdV-14]) occurred on a rural Southeast Alaska island. Nine patients requiredIn September 2008, an outbreak of pneumonia associated with an emerging human adenovirus (human adenovirus serotype 14 [HAdV-14]) occurred on a rural Southeast Alaska island. Nine patients required hospitalization, and 1 patient died. To investigate the outbreak, pneumonia case patients were matched to control participants on the basis of age, sex, and community of residence. Participants in the investigation and their household contacts were interviewed, and serum samples and respiratory tract specimens were collected. Risk factors were evaluated by means of conditional logistic regression. Among 32 pneumonia case patients, 21 (65%) had confirmed or probable HAdV-14 infection. None of 32 matched control participants had evidence of HAdV-14 infection (P<.001 for the difference). Factors independently associated with pneumonia included contact with a known HAdV-14-infected case patient (odds ratio [OR], 18.3 [95% confidence interval {CI}, >or=2.0]), current smoking (OR, 6.7 [95% CI, >or=0.9]), and having neither traveled off the island nor attended a large public gathering (OR, 14.7 [95% CI, >or=2.0]). Fourteen (67%) of 21 HAdV-14-positive case patients belonged to a single network of people who socialized and often smoked together and infrequently traveled off the island. HAdV-14 infection occurred in 43% of case-patient household contacts, compared with 5% of control-participant household contacts (P = .005). During a community outbreak in Alaska, HAdV-14 appeared to have spread mostly among close contacts and not widely in the community. Demographic characteristics and illness patterns among the case patients were similar to those observed in other recent outbreaks of HAdV-14 infection in the United States.

• Use of respiratory syncytial virus surveillance data to optimize the timing of immunoprophylaxis.

  Authors: Catherine A Panozzo, Lauren J Stockman, Aaron T Curns, Larry J Anderson

  Pediatrics. 07/2010; 126(1):e116-23.

  For children in the United States who are at high risk for severe respiratory syncytial virus (RSV) infection, the American Academy of Pediatrics (AAP) recommends administering immunoprophylaxisFor children in the United States who are at high risk for severe respiratory syncytial virus (RSV) infection, the American Academy of Pediatrics (AAP) recommends administering immunoprophylaxis during the RSV season. We present an approach to using surveillance data to help guide application of AAP recommendations for immunoprophylaxis to local patterns of RSV outbreaks. We analyzed data from laboratories that report consistently to the National Respiratory and Enteric Virus Surveillance System from 1992 to 2007. Local RSV seasons were defined and an immunoprophylaxis schedule was determined by using the median onset dates from each laboratory during 2002-2007. We applied these dates to 10 preceding years of RSV detection data. We compared how well the 5-year median-based method and a fixed date method were able to match the timing of immunoprophylaxis to the RSV season. Nineteen laboratories met our inclusion criteria and generally experienced only 1 RSV outbreak per season. Five years of data gave similar median onset/offset dates and season duration, as did 10 years and 15 years of data. The 5-year median schedule increased the number of seasons that children were protected at the season onset by 15% compared with a fixed start date of November 1 and identified communities that experienced RSV seasons with extended durations. The 5-year median method can be used to characterize timing of RSV seasons and optimally apply the current AAP recommendations for timing of palivizumab prophylaxis to the local community.

• Viral respiratory infections in hospitalized and community control children in Alaska.

  Authors: Rosalyn J Singleton, Lisa R Bulkow, Karen Miernyk, Carolynn DeByle, Lori Pruitt, Kimberlee Boyd Hummel, Dana Bruden, Janet A Englund, Larry J Anderson, Lynne Lucher, Robert C Holman, Thomas W Hennessy

  Journal of medical virology. 07/2010; 82(7):1282-90.

  Respiratory syncytial virus (RSV) in Alaska Native children from the Yukon Kuskokwim (YK) Delta is associated with a hospitalization rate five times higher than that reported for the general US childRespiratory syncytial virus (RSV) in Alaska Native children from the Yukon Kuskokwim (YK) Delta is associated with a hospitalization rate five times higher than that reported for the general US child population. The role of other viral respiratory pathogens has not been studied in this population. YK Delta children <3 years of age hospitalized with respiratory infections and same aged community control children were prospectively enrolled between October 2005 and September 2007. Polymerase chain reaction detection of viruses was performed on nasopharyngeal samples. Characteristics of hospitalized and asymptomatic control children were analyzed. From October 2005 to September 2007, 440 hospitalized and 425 control children were analyzed. Respiratory viruses were detected in 90% (395) of hospitalized children: 194 (44%) rhinovirus, 131 (30%) adenovirus, 102 (23%) RSV, 77 (18%) para influenza viruses (PIV), 66 (15%) human metapneumovirus (hMPV), 23 (5%) influenza, and 25 (6%) coronavirus. Fifty-two percent (221) of control children had a virus detected, most commonly rhinovirus (33%), and adenovirus (16%). RSV, PIV, hMPV, and influenza were significantly more common in hospitalized cases than control children, but rhinovirus, adenovirus, and coronavirus were not. RSV and hMPV were associated with higher severity of illness. In this study, RSV remains the most important virus associated with respiratory hospitalization, although hMPV and PIV were also common. RSV and hMPV were associated with more severe illness. Rhinovirus and adenovirus were detected in two-thirds of hospitalized children, but their frequent detection in control children made their role in respiratory hospitalization uncertain.

• Identification of adenoviruses in fecal specimens from wild chimpanzees (Pan trogylodytes schweinfurthii) in western Tanzania.

  Authors: Suxiang Tong, Jatinder Singh, Susan Ruone, Charles Humphrey, Cyril C Y Yip, Susanna K P Lau, Larry J Anderson, Taranjit Kaur

  The American journal of tropical medicine and hygiene. 05/2010; 82(5):967-70.

  DNA of two distinctive adenoviruses was detected in wild chimpanzees in western Tanzania that showed clinical signs of acute, upper respiratory disease, notably coughing. The amplified sequences fromDNA of two distinctive adenoviruses was detected in wild chimpanzees in western Tanzania that showed clinical signs of acute, upper respiratory disease, notably coughing. The amplified sequences from part of the capsid hexon gene suggests that one virus is a novel adenovirus serotype candidate and the other virus is a species C adenovirus most closely related to recent isolates from captive chimpanzees in the United States, Simian AdV 37 with 86% nucleic acid identity and Simian AdV 40 with 95% nucleic acid identity, respectively. The species C adenovirus sequences suggest possible recombination with a human adenovirus. The source of these viruses and disease association is not known.

• Health care transmission of a newly emergent adenovirus serotype in health care personnel at a military hospital in Texas, 2007.

  Authors: Fernanda C Lessa, Philip L Gould, Neil Pascoe, Dean D Erdman, Xiaoyan Lu, Michel L Bunning, Vincent C Marconi, Lisa Lott, Marc-Alain Widdowson, Larry J Anderson, Arjun Srinivasan

  The Journal of infectious diseases. 12/2009; 200(11):1759-65.

  BACKGROUND: Adenoviruses can cause outbreaks of febrile respiratory illness in military trainees, but until 2007, adenovirus serotype 14 (Ad14) was never associated with such outbreaks. From AprilBACKGROUND: Adenoviruses can cause outbreaks of febrile respiratory illness in military trainees, but until 2007, adenovirus serotype 14 (Ad14) was never associated with such outbreaks. From April through June 2007, 15 trainees at one base were hospitalized for pneumonia due to Ad14. Subsequent reports of febrile respiratory illness among health care personnel suggested nosocomial transmission. METHODS: Health care personnel participants completed a questionnaire and provided blood and nasal wash specimens for Ad14 diagnostic testing. We defined a confirmed case of Ad14 infection as one with titers > or = 1:80 or nasal wash specimens positive for Ad14 by polymerase chain reaction, whereas a possible case was defined by titers of 1:20 or 1:40. We also collected environmental samples. RESULTS: Among 218 tested health care personnel, 35 (16%) had titers > or = 1:20; of these, 7 had possible cases and 28 had confirmed cases of infection. Confirmed case patients were more likely to report febrile respiratory illness (57% vs 11%; P< .001) and to have had direct contact with patients with Ad14 infection (82% vs 62%; P.04 ). Of the 23 confirmed case patients with direct contact with Ad14-infected patients, 52% reported that patients were not in contact and droplet precautions at the time of exposure. Ad14 was recovered from several hospital surfaces. CONCLUSION: Our findings of possible nosocomial transmission of Ad14 highlight the need to reinforce infection control guidelines.

• Potent high-affinity antibodies for treatment and prophylaxis of respiratory syncytial virus derived from B cells of infected patients.

  Authors: Ellen J Collarini, F Eun-Hyung Lee, Orit Foord, Minha Park, Gizette Sperinde, Hai Wu, William D Harriman, Stephen F Carroll, Stote L Ellsworth, Larry J Anderson, Ralph A Tripp, Edward E Walsh, Bruce A Keyt, Lawrence M Kauvar

  Journal of immunology (Baltimore, Md. : 1950). 11/2009; 183(10):6338-45.

  Native human Abs represent attractive drug candidates; however, the low frequency of B cells expressing high-quality Abs has posed a barrier to discovery. Using a novel single-cell phenotypingNative human Abs represent attractive drug candidates; however, the low frequency of B cells expressing high-quality Abs has posed a barrier to discovery. Using a novel single-cell phenotyping technology, we have overcome this barrier to discover human Abs targeting the conserved but poorly immunogenic central motif of respiratory syncytial virus (RSV) G protein. For the entire cohort of 24 subjects with recent RSV infection, B cells producing Abs meeting these stringent specificity criteria were rare, <10 per million. Several of the newly cloned Abs bind to the RSV G protein central conserved motif with very high affinity (K(d) 1-24 pM). Two of the Abs were characterized in detail and compared with palivizumab, a humanized mAb against the RSV F protein. Relative to palivizumab, the anti-G Abs showed improved viral neutralization potency in vitro and enhanced reduction of infectious virus in a prophylaxis mouse model. Furthermore, in a mouse model for postinfection treatment, both anti-G Abs were significantly more effective than palivizumab at reducing viral load. The combination of activity in mouse models for both prophylaxis and treatment makes these high-affinity human-derived Abs promising candidates for human clinical testing.

• Vaccination to Induce Antibodies Blocking RSV G Protein CX3C-CX3CR1 Interaction Reduces Pulmonary Inflammation and Virus Replication in Mice.

  Authors: Wenliang Zhang, Youngjoo Choi, Lia M Haynes, Jennifer L Harcourt, Larry J Anderson, Les P Jones, Ralph A Tripp

  Journal of virology. 10/2009;

  Respiratory syncytial virus (RSV) infection causes substantial morbidity and some deaths in the young and elderly worldwide. There is no safe and effective vaccine available, although it is possibleRespiratory syncytial virus (RSV) infection causes substantial morbidity and some deaths in the young and elderly worldwide. There is no safe and effective vaccine available, although it is possible to reduce the hospitalization in high risk children with anti-RSV antibody prophylaxis. RSV has been shown to modify the immune response to infection, a feature linked in part to RSV G protein CX3C chemokine mimicry. This study determined if vaccination with G protein polypeptides or peptides spanning the central conserved region of the G protein could induce antibodies that blocked G protein CX3C-CX3CR1 interaction and disease pathogenesis mediated by RSV infection. The results show that mice vaccinated with G protein peptides or polypeptides containing the CX3C motif generate antibodies that inhibit G protein CX3C-CX3CR1 binding and chemotaxis, reduce lung virus titers, and prevent body weight loss and pulmonary inflammation. The results suggest that RSV vaccines that induce antibodies that block G protein CX3C-CX3CR1 interaction may offer a new safe and efficacious RSV vaccine strategy.

• Identification of a novel astrovirus (Astrovirus VA1) associated with an outbreak of acute gastroenteritis.

  Authors: Stacy R Finkbeiner, Yan Li, Susan Ruone, Christina Conrardy, Nicole Gregoricus, Denise Toney, Herbert W Virgin, Larry J Anderson, Jan Vinjé, David Wang, Suxiang Tong

  Journal of virology. 09/2009;

  The etiology of a large proportion of gastrointestinal illness is unknown. In this study, random Sanger sequencing and pyrosequencing approaches were used to analyze fecal specimens from aThe etiology of a large proportion of gastrointestinal illness is unknown. In this study, random Sanger sequencing and pyrosequencing approaches were used to analyze fecal specimens from a gastroenteritis outbreak of unknown etiology in a child care center. Multiple sequences with limited identity to known astroviruses were identified. Assembly of the sequences and subsequent RT-PCR and RACE experiments generated a complete genome of 6,586 nucleotides. Phylogenetic analysis demonstrated that this virus, named astrovirus VA1 (AstV-VA1), is highly divergent from all previously described astroviruses. Based on RT-PCR, specimens from multiple patients in this outbreak were unequivocally positive for Ast-VA1.