Emergence and Pandemic Potential of Avian Influenza A (H7N9) Virus

New genotypes of influenza A virus arise quickly and frequently around the world due to continued mutation and reassortment. Novel influenza A viruses pose a direct threat to immunologically naïve humans. A prime example is the recent emergence of avian-origin H7N9 viruses that have become enzootic in China. Three waves of the H7N9 breakout that began in March 2013 have resulted in 571 human cases and over 212 deaths as of 23 February 2015. Real-time influenza surveillance at the wild bird–human interface is essential to limit the outbreak in scale and geographic distribution and to understand the pandemic potential of the H7N9 avian influenza

NP and NS1 proteins of H5N1 virus significantly upregulated IFITM1, IFITM2, and IFITM3 in A549 cells

Background: Avian influence virus H5N1 causes serious public health concern with significant morbidity and mortality from poultry to humans. Interferon-induced transmembrane (IFITM) proteins usually protect cells from many virus infections by viral entry and replication.Objectives: The purpose of this study was to investigate whether H5N1 viral proteins involved in regulation IFITM1, IFITM2, and IFITM3 following H5N1 infection.Methods: NS1, M1, NP, PB2, HA and NA genes of H5N1 virus were generated by PCR and cloned into pcDNA3.1/myc-His (+) A vector for genes over-expression experiments. Gene expression levels was performed using Real-time PCR.Results: Research displayed that NS1, M1, NP, and PB2 proteins of H5N1 virus increased IFITM1, IFITM2, and IFITM3 expression in A549 cells, only IFITM1 was upregulated by M1 in HEK293T cells. However, our study did not find that HA and NA of H5N1 virus affected IFITM genes family or interferon genes expression.Conclusion: Taken together, our data suggested that IFITM1, IFITM2, and IFITM3 might be directly upregulated via NS1, M1, NP, and PB2 proteins during H5N1 avian influenza virus infection. This study provided new insights into the influence of NS1 and NP proteins on regulation of IFITM1, IFITM2, and IFITM3 expression following H5N1 infection.Keywords: Influenza Virus, H5N1, NS1 protein, NP protein, IFITMs

Induced Susceptibility of Host Is Associated with an Impaired Antioxidant System Following Infection with Cryptosporidium parvum in Se-Deficient Mice

BACKGROUND: Susceptibility or resistance to infection with Cryptosporidium parvum (C.parvum) correlates with Selenium (Se) deficiency in response to infection. Both adult Se-adequate and Se-deficient mouse models of cryptosporidiosis were used to study the cell-mediated immune response during the course of C. parvum infection. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples from mouse models were used for Se status. The concentration of MDA, SOD, GPx and CAT in blood has revealed that lower Se level exist in Se-deficient mice. Mesenteric lymph node (MLN) lymphocytes from both mouse models were proliferated after ex vivo re-stimulation with C. parvum sporozoite antigen. The study of the cytokine profiles from the supernatant of proliferated MLN cells revealed that Se-adequate mice produced higher levels of Th1 (IFN-gamma and IL-2) and moderate amounts of Th2 (IL-4) cytokines throughout the course of infection. Whereas, MLN cells from Se-deficient mice produced lower levels of IFN-gamma, IL-2 and IL-4 cytokines. The counts of total white cell and CD3, CD4, CD8 cell in Se-adequate were higher than that in Se-deficient mice. SIGNIFICANCE: These results suggest that Cell immunity is affected by Se status after infection with C. parvum from kinetic changes of different white cells and cytokine. In conclusion, induced susceptibility of host is associated with an impaired antioxidant system following infection with C. parvum in C57BL/6 Selenium deficient mice

Selenium deficiency impairs host innate immune response and induces susceptibility to Listeria monocytogenes infection

<p>Abstract</p> <p>Background</p> <p>Susceptibility or resistance to infection with <it>Listeria monocytogenes </it>correlates with Selenium (Se) deficiency in response to infection.</p> <p>Results</p> <p>Se-deficient mouse models of listeriosis were used to study the innate immune response during the course of <it>L. monocytogenes </it>infection. Blood samples from mouse models were used for Se status. The concentration of MDA, SOD, GPx and CAT in blood has revealed that lower Se level exist in Se-deficient mice. Intestine, mesenteric lymph node, liver, spleen and brain from each mouse were to study the bacterial burden in organs. The analysis of cell types of spleen from Se-deficient mice revealed that the ability of the host to elicit a rapid recruitment and activation of systemic innate immune response to infection was to a certain extent compromised under conditions of Se deficiency. The cytokine levels in the serum and cytokine expression levels in the livers from Se-deficient mice revealed that the innate immune response of Se-deficient mice was impaired throughout the course of infection. These results suggest that innate immune response is altered by Se deficiency after infection with <it>L. monocytogenes</it>.</p> <p>Conclusion</p> <p>In conclusion, induced susceptibility of host resistance is associated with an impaired innate immune response following infection with <it>L. monocytogenes </it>in C57BL/6 Se-deficient mice.</p

Parasite Species Associated With Wild Plateau Pika (Ochotona Curzoniae) In Southeastern Qinghai Province, China

A survey was conducted to determine the prevalence and seasonal abundance of egg, larval, and adult stages of helminths; oocyts of protozoans; and ectoparasites of plateau pikas (Ochotona curzoniae) in seven areas of southeastern Qinghai Province, China, during August 2006 and May 2007. Fecal samples collected from 430 plateau pikas were examined by the modified McMaster technique, which revealed that 83% of the samples contained eggs from two or more helminth species. Mean fecal egg counts were generally moderate and showed the same trend irrespective of the age or sex of the pikas. The prevalence and counts of cestode eggs showed strong seasonal relationships that corresponded with the rainfall pattern in the study area during the study period. Of the 430 plateau pika examined at necropsy, 89% contained adult nematode or cestode species, but none of these contained adult trematode species or protozoans. Overall, six genera of adult nematodes including Oesophagostomum sp., Cephaluris coloradensis, Eugenuris schumakowiescsi, Haemonchus sp., Trichuris sp., and Chbertiinae sp.; three genera of adult cestodes including Schizorchis sp., Ochotonae sp., and Hymenolepis nana; three ectoparasite species including Hypoderma curzonial, Pulex sp., and Ixodes ovatus; and one proscolex stage of a cestode, Echinococcus multilocularis or Echinococcus shiquicus, were encountered during the study. Other genera examined occurred in low numbers, which did not allow any meaningful comparisons. Overall, results suggest that four parasite species, Hypoderma curzonial, Pulex sp., Ixodes ovatus Neumann, and Cephaluris coloradensis, may be regulating factors in controlling future numbers of plateau pika in this study area. These data provide evidence of a natural biologic control mechanism of plateau pika on grassland habitats, and may be of use for identifying the mechanism of transmission of parasites between plateau pika, livestock, and humans

NP and NS1 proteins of H5N1 virus significantly upregulated IFITM1, IFITM2, and IFITM3 in A549 cells

Background: Avian influence virus H5N1 causes serious public health concern with significant morbidity and mortality from poultry to humans. Interferon-induced transmembrane (IFITM) proteins usually protect cells from many virus infections by viral entry and replication. Objectives: The purpose of this study was to investigate whether H5N1 viral proteins involved in regulation IFITM1, IFITM2, and IFITM3 following H5N1 infection. Methods: NS1, M1, NP, PB2, HA and NA genes of H5N1 virus were generated by PCR and cloned into pcDNA3.1/myc-His (+) A vector for genes over-expression experiments. Gene expression levels was performed using Real-time PCR. Results: Research displayed that NS1, M1, NP, and PB2 proteins of H5N1 virus increased IFITM1, IFITM2, and IFITM3 expression in A549 cells, only IFITM1 was upregulated by M1 in HEK293T cells. However, our study did not find that HA and NA of H5N1 virus affected IFITM genes family or interferon genes expression. Conclusion: Taken together, our data suggested that IFITM1, IFITM2, and IFITM3 might be directly upregulated via NS1, M1, NP, and PB2 proteins during H5N1 avian influenza virus infection. This study provided new insights into the influence of NS1 and NP proteins on regulation of IFITM1, IFITM2, and IFITM3 expression following H5N1 infection. DOI: https://dx.doi.org/10.4314/ahs.v19i1.13 Cite as: Wang H, Chen L, Luo J, H H. NP and NS1 proteins of H5N1 virus significantly upregulated IFITM1, IFITM2, and IFITM3 in A549 cells. Afri Health Sci. 2019;19(1). 1402-1410. https://dx.doi.org/10.4314/ahs.v19i1.1

Novel Variants Identified in Multiple Sclerosis Patients From Southern China

Background: Multiple sclerosis (MS) is an autoimmune and demyelinating disease. Genome-wide association studies have shown that MS is associated with many genetic variants in some human leucocyte antigen genes and other immune-related genes, however, those studies were mostly specific to Caucasian populations. We attempt to address whether the same associations are also true for Asian populations by conducting whole-exome sequencing on MS patients from southern China.Methods: Genomic DNA was extracted from the peripheral blood mononucleocytes of 8 MS patients and 26 healthy controls and followed by exome sequencing.Results: In total, 41,227 variants were found to have moderate to high impact on their protein products. After filtering per allele frequencies according to known database, 17 variants with the allele frequency &lt;1% or variants with undetermined frequency were identified to be unreported and have significantly different frequencies between the MS patients and healthy controls. After validation via Sanger sequencing, one rare variant located in exon 7 of TRIOBP (Chr22: 37723520G&gt;T, Ala322Ser, rs201693690) was found to be a novel missense variant.Conclusion: MS in southern China may have association with unique genetic variants, our data suggest TRIOBP as a potential novel risk gene

Reassortant H9N2 Influenza Viruses Containing H5N1-Like PB1 Genes Isolated from Black-Billed Magpies in Southern China

H9N2 influenza A viruses have become endemic in different types of terrestrial poultry and wild birds in Asia, and are occasionally transmitted to humans and pigs. To evaluate the role of black-billed magpies (Pica pica) in the evolution of influenza A virus, we conducted two epidemic surveys on avian influenza viruses in wild black-billed magpies in Guangxi, China in 2005 and characterized three isolated black-billed magpie H9N2 viruses (BbM viruses). Phylogenetic analysis indicated that three BbM viruses were almost identical with 99.7 to 100% nucleotide homology in their whole genomes, and were reassortants containing BJ94-like (Ck/BJ/1/94) HA, NA, M, and NS genes, SH/F/98-like (Ck/SH/F/98) PB2, PA, and NP genes, and H5N1-like (Ck/YN/1252/03, clade 1) PB1 genes. Genetic analysis showed that BbM viruses were most likely the result of multiple reassortments between co-circulating H9N2-like and H5N1-like viruses, and were genetically different from other H9N2 viruses because of the existence of H5N1-like PB1 genes. Genotypical analysis revealed that BbM viruses evolved from diverse sources and belonged to a novel genotype (B46) discovered in our recent study. Molecular analysis suggested that BbM viruses were likely low pathogenic reassortants. However, results of our pathogenicity study demonstrated that BbM viruses replicated efficiently in chickens and a mammalian mouse model but were not lethal for infected chickens and mice. Antigenic analysis showed that BbM viruses were antigenic heterologous with the H9N2 vaccine strain. Our study is probably the first report to document and characterize H9N2 influenza viruses isolated from black-billed magpies in southern China. Our results suggest that black-billed magpies were susceptible to H9N2 influenza viruses, which raise concerns over possible transmissions of reassortant H9N2 viruses among poultry and wild birds

Reassortant H9N2 Influenza Viruses Containing H5N1- Like PB1 Genes Isolated from Black-Billed Magpies in Southern China

H9N2 influenza A viruses have become endemic in different types of terrestrial poultry and wild birds in Asia, and are occasionally transmitted to humans and pigs. To evaluate the role of black-billed magpies (Pica pica) in the evolution of influenza A virus, we conducted two epidemic surveys on avian influenza viruses in wild black-billed magpies in Guangxi, China in 2005 and characterized three isolated black-billed magpie H9N2 viruses (BbM viruses). Phylogenetic analysis indicated that three BbM viruses were almost identical with 99.7 to 100% nucleotide homology in their whole genomes, and were reassortants containing BJ94-like (Ck/BJ/1/94) HA, NA, M, and NS genes, SH/F/98-like (Ck/SH/F/98) PB2, PA, and NP genes, and H5N1-like (Ck/YN/1252/03, clade 1) PB1 genes. Genetic analysis showed that BbM viruses were most likely the result of multiple reassortments between co-circulating H9N2-like and H5N1-like viruses, and were genetically different from other H9N2 viruses because of the existence of H5N1-like PB1 genes. Genotypical analysis revealed that BbM viruses evolved from diverse sources and belonged to a novel genotype (B46) discovered in our recent study. Molecular analysis suggested that BbM viruses were likely low pathogenic reassortants. However, results of our pathogenicity study demonstrated that BbM viruses replicated efficiently in chickens and a mammalian mouse model but were not lethal for infected chickens and mice. Antigenic analysis showed that BbM viruses were antigenic heterologous with the H9N2 vaccine strain. Our study is probably the first report to document and characterize H9N2 influenza viruses isolated from black-billed magpies in southern China. Our results suggest that black-billed magpies were susceptible to H9N2 influenza viruses, which raise concerns over possible transmissions of reassortant H9N2 viruses among poultry and wild birds