ABSTRACT: Understanding the pathogenesis of influenza infection is a key factor leading to the prevention and control of future outbreaks. Pandemic 2009 Influenza H1N1 infection, although frequently mild, led to a severe and fatal form of disease in certain cases that make its virulence nature debatable. Much effort has been made toward explaining the determinants of disease severity; however, no absolute reason has been established.
This study presents the heterogeneous virulence of clinically similar strains of pandemic 2009 influenza virus in human alveolar adenocarcinoma cells and mice. The viruses were obtained from patients who were admitted in a local hospital in China with a similar course of infection and recovered. The A/Nanchang/8002/2009 and A/Nanchang/8011/2009 viruses showed efficient replication and high lethality in mice while infection with A/Nanchang/8008/2009 was not lethal with impaired viral replication, minimal pathology and modest proinflammatory activity in lungs. Sequence analysis displayed prominent differences between polymerase subunits (PB2 and PA) of viral genomes that might correlate with their different phenotypic behavior.
The study confirms that biological heterogeneity, linked with the extent of viral replication, exists among pandemic H1N1 strains that may serve as a benchmark for future investigations on influenza pathogenesis.
Virology Journal 06/2012; 9:104. · 2.34 Impact Factor
ABSTRACT: The WNT1-inducible signaling pathway protein 3 (WISP3), which belongs to the CCN (cysteine-rich protein 61, connective tissue growth factor, nephroblastoma overexpressed) family, is a secreted cysteine-rich matricellular protein that is involved in chondrogenesis, osteogenesis and tumorigenesis. WISP3 gene mutations are associated with progressive pseudorheumatoid dysplasia (PPD, OMIM208230), an autosomal recessive genetic disease that is characterized by the swelling of multiple joints and disproportionate dwarfism.
Four PPD patients from two unrelated Chinese families were recruited for this study. The clinical diagnosis was confirmed by medical history, physical examinations, laboratory results and radiological abnormalities. WISP3 mutations were detected by direct DNA sequence analysis. In total, four different mutations were identified, which consisted of two missense mutations, one deletion and one insertion that spanned exons 3, 5 and 6 of the WISP3 gene. One of the missense mutations (c.342T>G/p.C114W) and a seven-base pair frameshift deletion (c.716_722del/p.E239fs*16) were novel. The other missense mutation (c.1000T>C/p. S334P) and the insertion mutation (c.866_867insA/p.Q289fs*31) had previously been identified in Chinese patients. All four cases had a compound heterozygous status, and their parents were heterozygous carriers of these mutations.
The results of our study expand the spectrum of WISP3 mutations that are associated with PPD and further elucidate the function of WISP3.
PLoS ONE 01/2012; 7(6):e38643. · 4.09 Impact Factor
ABSTRACT: South China has a proven role in the global epidemiology of previous influenza outbreaks due to its dual seasonal pattern. We present the virologic, genetic and clinical characterization of pandemic H1N1 influenza infection (pH1N1) in Shantou and Nanchang, cities in southern China, during the second wave of the 2009-2010 pandemic.
Nasopharyngeal swabs were collected from 165 individuals with influenza-like illness (ILI) who presented to the hospitals in Shantou and Nanchang. Laboratory diagnosis and characterization was performed by real-time PCR, virus isolation in embryonated chicken eggs, and sequencing.
pH1N1 activity was sustained in three different temporal patterns throughout the study period. The overall positivity rate of pH1N1 was 50% with major distribution among young adults between the ages of 13 and 30 years. High fever, cough, expectoration, chest pain, myalgia, nasal discharge and efficient viral replication were observed as major clinical markers whereas a substantial number of afebrile cases (17%) was also observed. Rate of hospitalization and disease severity (39%) and recovery (100%) were also high within the region. Furthermore, severe complications were likely to develop in young adults upon pH1N1 infection. Genetic characterization of the HA and NA genes of pH1N1 strains exhibited homogenous spread of pH1N1 strains with 99% identity with prototypic strains; however, minor unique mutations were also observed in the HA gene.
The study illustrates the detailed characteristics of 2009 influenza pandemic in southern parts of China that might help to strategize preparedness for future pandemics and subsequent influenza seasons.
The Journal of Infection in Developing Countries 10/2011; 5(10):700-10. · 1.19 Impact Factor