The significance of avian influenza virus mouse-adaptation and its application in characterizing the efficacy of new vaccines and therapeutic agents

Due to the increased frequency of interspecies transmission of avian influenza viruses, studies designed to identify the molecular determinants that could lead to an expansion of the host range have been increased. A variety of mouse-based mammalian-adaptation studies of avian influenza viruses have provided insight into the genetic alterations of various avian influenza subtypes that may contribute to the generation of a pandemic virus. To date, the studies have focused on avian influenza subtypes H5, H6, H7, H9, and H10 which have recently caused human infection. Although mice cannot fully reflect the course of human infection with avian influenza, these mouse studies can be a useful method for investigating potential mammalian adaptive markers against newly emerging avian influenza viruses. In addition, due to the lack of appropriate vaccines against the diverse emerging influenza viruses, the generation of mouse-adapted lethal variants could contribute to the development of effective vaccines or therapeutic agents. Within this review, we will summarize studies that have demonstrated adaptations of avian influenza viruses that result in an altered pathogenicity in mice which may suggest the potential application of mouse-lethal strains in the development of influenza vaccines and/or therapeutics in preclinical studies.

Phylogenetic Analysis of the 56-kDa Type-Specific Protein Genes of Orientia tsutsugamushi in Central Korea

There are several antigenic variants of Orientia tsutsugamushi. The 56-kDa type-specific antigen (TSA) is responsible for the antigenic variation. Nucleotide sequences of the 56-kDa TSA obtained from 44 eschar samples of Korean scrub typhus patients and from 40 representative strains retrieved from the GenBank database were analyzed phylogenetically. Clinical patient data were assessed based on the genotyping results. Of the 44 nucleotide sequences, 32 (72.7%) clustered with the Boryong genotype, which is the major genotype in Korea. Eleven nucleotide sequences (25%) clustered with the Kawasaki genotype, not identified in Korea until 2010. One nucleotide sequence was consistent with the Karp genotype. The clinical course of the patients infected with each genotype showed no differences. Diagnostic performance of the immunofluorescence assay (IFA) using the 56-kDa TSA from Gilliam, Karp and Boryong as test antigens were not different for the Boryong and Kawasaki genotypes. Although Boryong is still the predominant genotype, the results suggest that Kawasaki genotype is quite prevalent in Chungbuk province of Korea.

Phylogenetic Analysis of the 56-kDa Type-Specific Protein Genes of Orientia tsutsugamushi in Central Korea

There are several antigenic variants of Orientia tsutsugamushi. The 56-kDa type-specific antigen (TSA) is responsible for the antigenic variation. Nucleotide sequences of the 56-kDa TSA obtained from 44 eschar samples of Korean scrub typhus patients and from 40 representative strains retrieved from the GenBank database were analyzed phylogenetically. Clinical patient data were assessed based on the genotyping results. Of the 44 nucleotide sequences, 32 (72.7%) clustered with the Boryong genotype, which is the major genotype in Korea. Eleven nucleotide sequences (25%) clustered with the Kawasaki genotype, not identified in Korea until 2010. One nucleotide sequence was consistent with the Karp genotype. The clinical course of the patients infected with each genotype showed no differences. Diagnostic performance of the immunofluorescence assay (IFA) using the 56-kDa TSA from Gilliam, Karp and Boryong as test antigens were not different for the Boryong and Kawasaki genotypes. Although Boryong is still the predominant genotype, the results suggest that Kawasaki genotype is quite prevalent in Chungbuk province of Korea.

Clinical characteristics of acute lower respiratory tract infections due to 13 respiratory viruses detected by multiplex PCR in children / 소아과

PURPOSE: This study was performed to investigate the epidemiologic and clinical features of 13 respiratory viruses in children with acute lower respiratory tract infections (ALRIs). METHODS: Nasopharyngeal aspirates were prospectively obtained from 325 children aged 15 years or less from May 2008 to April 2009 and were tested for the presence of 13 respiratory viruses by multiplex real-time-polymerase chain reaction (RT-PCR). RESULTS: Viruses were identified in 270 children (83.1%). Co-infections with > or =2 viruses were observed in 71 patients (26.3%). Respiratory syncytial virus (RSV) was the most common virus detected (33.2%), followed by human rhinovirus (hRV) (19.1%), influenza virus (Flu A) (16.9%), human metapneumovirus (hMPV) (15.4%), parainfluenza viruses (PIVs) (8.3%), human bocavirus (hBoV) (8.0%), adenovirus (ADV) (5.8%), and human coronavirus (hCoV) (2.2%). Clinical diagnoses of viral ALRIs were bronchiolitis (37.5%), pneumonia (34.5%), asthma exacerbation (20.9%), and croup (7.1%). Clinical diagnoses of viral bronchiolitis and pneumonia were frequently demonstrated in patients who tested positive for RSV, hRV, hMPV, or Flu A. Flu A and hRV were most commonly identified in children older than 3 years and were the 2 leading causes of asthma exacerbation. hRV C was detected in 14 (4.3%) children, who were significantly older than those infected with hRV A (mean+/-SD, 4.1+/-3.5 years vs. 1.7+/-2.3 years; P=0.009). hBoV was usually detected in young children (2.3+/-3.4 years) with bronchiolitis and pneumonia. CONCLUSION: This study described the features of ALRI associated with 13 respiratory viruses in Korean children. Additional investigations are required to define the roles of newly identified viruses in children with ALRIs.

Genetic Characteristics and Phylogenetic Analysis of Influenza Type B Viruses Isolated from Nasopharyngeal Suction Samples of Korean Patients

To investigate the genetic characteristics of human influenza type B viruses circulating in Chungbuk province, Korea, we tested 510 clinical samples of nasopharyngeal suction from pediatric patients diagnosed with respiratory illness between June 2007 and June 2008. Twelve out of thirty-six isolates were identified as type B influenza virus by RT-PCR and sequencing analysis. Interestingly, genetic characterization of type B viruses isolated in this study revealed that all type B influenza viruses were the Yamagata lineages, a vaccine strains of southern hemisphere during 2007~2008, rather than the Victoria lineage of northern hemisphere during 2007~2008. Furthermore, there were a total of twelve unique mutations (HA: H40Y, D/G230S, V252M and K272R and NA: P3H, P/T/S42Q, N59S) occurred in our type B isolates. These results suggest that relative high prevalence of type B viruses in Korea during 2007~2008 season might be due to the wrong vaccine strains selection. Taken together, the results of this study demonstrate continuous evolutions of human type B viruses by antigenic drift and also highlight the need to closely monitoring of influenza viruses to aid the early detection of potentially pandemic strains as well as underscore the need for new therapeutics.