Venkata R. Duvvuri

Genetic Variability of Human Respiratory Syncytial Virus A Strains Circulating in Ontario: A Novel Genotype with a 72 Nucleotide G Gene Duplication

Human respiratory syncytial virus (HRSV) is the main cause of acute lower respiratory infections in children under 2 years of age and causes repeated infections throughout life. We investigated the genetic variability of RSV-A circulating in Ontario during 2010–2011 winter season by sequencing and phylogenetic analysis of the G glycoprotein gene. Among the 201 consecutive RSV isolates studied, RSV-A (55.7%) was more commonly observed than RSV-B (42.3%). 59.8% and 90.1% of RSV-A infections were among children ≤12 months and ≤5 years old, respectively. On phylogenetic analysis of the second hypervariable region of the 112 RSV-A strains, 110 (98.2%) clustered within or adjacent to the NA1 genotype; two isolates were GA5 genotype. Eleven (10%) NA1-related isolates clustered together phylogenetically as a novel RSV-A genotype, named ON1, containing a 72 nucleotide duplication in the C-terminal region of the attachment (G) glycoprotein. The predicted polypeptide is lengthened by 24 amino acids and includes a23 amino acid duplication. Using RNA secondary structural software, a possible mechanism of duplication occurrence was derived. The 23 amino acid ON1 G gene duplication results in a repeat of 7 potential O-glycosylation sites including three O-linked sugar acceptors at residues 270, 275, and 283. Using Phylogenetic Analysis by Maximum Likelihood analysis, a total of 19 positively selected sites were observed among Ontario NA1 isolates; six were found to be codons which reverted to the previous state observed in the prototype RSV-A2 strain. The tendency of codon regression in the G-ectodomain may infer a decreased avidity of antibody to the current circulating strains. Further work is needed to document and further understand the emergence, virulence, pathogenicity and transmissibility of this novel RSV-A genotype with a72 nucleotide G gene duplication.

Estimated Effects of Projected Climate Change on the Basic Reproductive Number of the Lyme Disease Vector Ixodes scapularis

Background: The extent to which climate change may affect human health by increasing risk from vector-borne diseases has been under considerable debate. Objectives: We quantified potential effects of future climate change on the basic reproduction number (R0) of the tick vector of Lyme disease, Ixodes scapularis, and explored their importance for Lyme disease risk, and for vector-borne diseases in general. Methods: We applied observed temperature data for North America and projected temperatures using regional climate models to drive an I. scapularis population model to hindcast recent, and project future, effects of climate warming on R0. Modeled R0 increases were compared with R0 ranges for pathogens and parasites associated with variations in key ecological and epidemiological factors (obtained by literature review) to assess their epidemiological importance. Results: R0 for I. scapularis in North America increased during the years 1971–2010 in spatio-temporal patterns consistent with observations. Increased temperatures due to projected climate change increased R0 by factors (2–5 times in Canada and 1.5–2 times in the United States), comparable to observed ranges of R0 for pathogens and parasites due to variations in strains, geographic locations, epidemics, host and vector densities, and control efforts. Conclusions: Climate warming may have co-driven the emergence of Lyme disease in northeastern North America, and in the future may drive substantial disease spread into new geographic regions and increase tick-borne disease risk where climate is currently suitable. Our findings highlight the potential for climate change to have profound effects on vectors and vector-borne diseases, and the need to refocus efforts to understand these effects. Citation: Ogden NH, Radojević M, Wu X, Duvvuri VR, Leighton PA, Wu J. 2014. Estimated effects of projected climate change on the basic reproductive number of the Lyme disease vector Ixodes scapularis. Environ Health Perspect 122:631–638; http://dx.doi.org/10.1289/ehp.1307799

Genetic diversity and evolutionary insights of respiratory syncytial virus A ON1 genotype: global and local transmission dynamics

Human respiratory syncytial virus (RSV) A ON1 genotype, first detected in 2010 in Ontario, Canada, has been documented in 21 countries to date. This study investigated persistence and transmission dynamics of ON1 by grouping 406 randomly selected RSV-positive specimens submitted to Public Health Ontario from August 2011 to August 2012; RSV-A-positive specimens were genotyped. We identified 370 RSV-A (181 NA1, 135 NA2, 51 ON1 3 GA5) and 36 RSV-B positive specimens. We aligned time-stamped second hypervariable region (330 bp) of G-gene sequence data (global, n = 483; and Ontario, n = 60) to evaluate transmission dynamics. Global data suggests that the most recent common ancestor of ON1 emerged during the 2008–2009 season. Mean evolutionary rate of the global ON1 was 4.10 × 10−3 substitutions/site/year (95% BCI 3.1–5.0 × 10−3), not significantly different to that of Ontario ON1. The estimated mean reproductive number (R0 = ∼ 1.01) from global and Ontario sequences showed no significant difference and implies stability among global RSV-A ON1. This study suggests that local epidemics exhibit similar underlying evolutionary and epidemiological dynamics to that of the persistent global RSV-A ON1 population. These findings underscore the importance of continual molecular surveillance of RSV in order to gain a better understanding of epidemics.

Role of Positive Selection Pressure on the Evolution of H5N1 Hemagglutinin

The surface glycoprotein hemagglutinin (HA) helps the influenza A virus to evade the host immune system by antigenic variation and is a major driving force for viral evolution. In this study, the selection pressure on HA of H5N1 influenza A virus was analyzed using bioinformatics algorithms. Most of the identified positive selection (PS) sites were found to be within or adjacent to epitope sites. Some of the identified PS sites are consistent with previous experimental studies, providing further support to the biological significance of our findings. The highest frequency of PS sites was observed in recent strains isolated during 2005–2007. Phylogenetic analysis was also conducted on HA sequences from various hosts. Viral drift is almost similar in both avian and human species with a progressive trend over the years. Our study reports new mutations in functional regions of HA that might provide markers for vaccine design or can be used to predict isolates of pandemic potential.

Developing a temperature-driven map of the basic reproductive number of the emerging tick vector of Lyme disease Ixodes scapularis in Canada

A mechanistic model of the tick vector of Lyme disease, Ixodes scapularis, was adapted to a deterministic structure. Using temperature normals smoothed by Fourier analysis to generate seasonal temperature-driven development rates and host biting rates, and a next generation matrix approach, the model was used to obtain values for the basic reproduction number (R(0)) for I. scapularis at locations in southern Canada where the tick is established and emerging. The R(0) at Long Point, Point Pelee and Chatham sites where I. scapularis are established, was estimated at 1.5, 3.19 and 3.65, respectively. The threshold temperature conditions for tick population survival (R(0)=1) were shown to be the same as those identified using the mechanistic model (2800-3100 cumulative annual degree days >0°C), and a map of R(0) for I. scapularis, the first such map for an arthropod vector, was drawn for Canada east of the Rocky Mountains. This map supports current risk assessments for Lyme disease risk emergence in Canada. Sensitivity analysis identified host abundance, tick development rates and summer temperatures as highly influential variables in the model, which is consistent with our current knowledge of the biology of this tick. The development of a deterministic model for I. scapularis that is capable of providing values for R(0) is a key step in our evolving ability to develop tools for assessment of Lyme disease risk emergence and for development of public health policies on surveillance, prevention and control.

Highly conserved cross-reactive CD4+ T-cell HA-epitopes of seasonal and the 2009 pandemic influenza viruses.

Please cite this paper as: Duvvuri et al. (2010) Highly conserved cross‐reactive CD4+ T‐cell HA‐epitopes of seasonal and the 2009 pandemic influenza viruses. Influenza and Other Respiratory Viruses 4(5), 249–258.

Altered spectrum of somatic hypermutation in common variable immunodeficiency disease characteristic of defective repair of mutations

Pathogenic common variable immunodeficiency diseases (CVID) are genetic, usually inherited diseases for which a limited number of genetic defects have been implicated. As CVID presents with a wide range of clinical characteristics, there are likely diverse and for the most part unidentified genetic causes. In some individuals, defects in somatic hypermutation (SHM) have been suggested as the underlying cause of CVID. To address the mechanisms of SHM defects in CVID, we conducted a comprehensive mutational analysis of immunoglobulin heavy chain sequences from CVID patients. We identified several remarkably specific alterations in the spectra of SHM in comparison to healthy individuals. We provide evidence that some CVID cases are associated with defective repair of AID-induced mutations by the DNA mismatch repair (MMR) machinery. Our findings together with reports of increased chromosomal radiosensitivity and associated lymphoproliferative disorders amongst CVID patients, suggest that altered DNA damage repair may be a cause of CVID.

Information and communication technology developments in asthma management: A systematic review

This review aims to explain the progress of information and communication technology (ICT) applications in asthma management. Appropriate literature was printed out from the bibliographic databases and library source using relevant key phrases of ICT and asthma. The ICT developments from simple to complex modules to augment the conventional methods of asthma care with a caution of excessive reliance upon technology were discussed. However, it should be noted ICTs are for maximizing the human clinicians own ability to receive and process information as well as providing unique opportunities for patients, physicians, pharmacists and researchers.

Genetic characterization of seasonal influenza A (H3N2) viruses in Ontario during 2010–2011 influenza season: high prevalence of mutations at antigenic sites

The direct effect of antigenic site mutations in influenza viruses on antigenic drift and vaccine effectiveness is poorly understood.

Human metapneumovirus prevalence and molecular epidemiology in respiratory outbreaks in Ontario, Canada

Human metapneumovirus (hMPV) has been identified previously as a cause of respiratory outbreaks in adults, including the elderly. The objective of this study was to document respiratory outbreaks that were caused by hMPV in Ontario, Canada and to identify the various circulating genotypes during April 2009–February 2012. The majority of the outbreaks that were part of this study were in adults (>65 years). Total nucleic acid extraction was done on 123 residual anonymized clinical specimens from 51 different respiratory outbreaks. Specimens were subjected to PCR amplification and Sanger sequencing targeting the F and G genes of hMPV. Phylogenetic analysis was performed to identify genotypes. HMPV accounted for 195 (8.5%) of 2,292 respiratory outbreaks. Genotype A2b was most prevalent, detected in 28 (54.9%) of 51 typed hMPV‐positive outbreaks. The genotype A2b2 that was described recently was also identified. In earlier reports, subtype A1 was reported in Canada which was absent in the specimens typed in this study. This shift in genotype may be significant in terms of disease severity, and for any future vaccine considerations. Regular testing for hMPV should be done as part of outbreak investigation. J. Med. Virol. 87:269–274, 2015.