Heilongjiang Provincial Key Laboratory for Infection and Immunity

Harbin, China

Heilongjiang Provincial Key Laboratory for Infection and Immunity

Harbin, China
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Wang J.,Heilongjiang Provincial Key Laboratory for Infection and Immunity | Zhang C.-L.,Harbin Medical University | Zhang C.-L.,Harbin Chest Hospital | Ji B.-Y.,Harbin Medical University | And 12 more authors.
Journal of Clinical Microbiology | Year: 2011

For the last decade China has occupied second place, after India, among the top five countries with high burdens of tuberculosis (TB). Heilongjiang Province is located in northeastern China. The prevalence of drug-resistant TB in Heilongjiang Province is higher than the average level in China. To determine the transmission characteristics of Mycobacterium tuberculosis strains isolated in this area and their genetic relationships, especially among the Beijing family strains, we investigated their genotypes. From May 2007 to October 2008, 200 M. tuberculosis isolates from patients presenting pulmonary TB were analyzed by molecular typing using PCR-based methods: spacer-oligonucleotide typing (spoligotyping), Beijing family-specific PCR (detection of the deletion of region of difference 105 [RD105]), and mycobacterial interspersed repetitive-unitvariable- number tandem-repeat (MIRU-VNTR) analysis. Different combinations of MIRU-VNTR loci were evaluated to define the genotypes and clustering characteristics of the local strains. We found that Beijing family strains represented 89.5% of the isolates studied. However, the rates of multidrug-resistant (MDR) M. tuberculosis among Beijing and non-Beijing family strains were not statistically different. The 15-locus set is considered the optimal MIRU-VNTR locus combination for analyzing the M. tuberculosis strains epidemic in this area, while the 10-locus set is an ideal set for first-line molecular typing. We found that the clustering rate of all the M. tuberculosis isolates analyzed was 10.0% using the 15-locus set typing. We conclude that the Beijing family genotype is predominant and that highly epidemic TB and MDR TB are less likely associated with the active transmission of M. tuberculosis in the study area. Copyright © 2011, American Society for Microbiology.

Liu A.,Harbin Medical University | Liu A.,Heilongjiang Provincial Key Laboratory for Infection and Immunity | Ji H.,Harbin Medical University | Ji H.,Heilongjiang Provincial Key Laboratory for Infection and Immunity | And 10 more authors.
Parasitology Research | Year: 2011

Contamination of the water supply by protozoa often causes outbreaks of cryptosporidiosis and giardiasis. The goals of the present study was to investigate the level of Cryptosporidium and Giardia duodenalis in wastewater from wastewater treatment plants in Harbin, China, and to understand the endemic transmission characteristics of cryptosporidiosis and giardiasis. Forty-eight domestic wastewater specimens from the two wastewater treatment plants in Harbin City were collected from April 2009 to March 2010. Cryptosporidium spp. and G. duodenalis assemblages were identified by PCR and sequencing of the 18S ribosomal RNA and the triosephosphate isomerase genes, respectively. In total, 15 wastewater specimens were PCR positive for Cryptosporidium and 23 were PCR positive for G. duodenalis. The prevalence of contamination with G. duodenalis (47.9%) was higher than that of Cryptosporidium (31.3%). Molecular identification showed the presence of two Cryptosporidium spp. (14 belonging to Cryptosporidium andersoni and one belonging to Cryptosporidium ubiquitum) and two G. duodenalis assemblages (18 belonging to assemblage AII and six belonging to assemblage B). In addition, eight specimens contained both Cryptosporidium and G. duodenalis, and one specimen contained G. duodenalis assemblages AII and B. These results suggested humans might be the primary source of G. duodenalis contamination in wastewater in the studied area. In contrast, a low prevalence of C. ubiquitum suggested a reduced risk of human cryptosporidiosis caused by C. ubiquitum via waterborne route. This work provides basic experimental data needed for local wastewater treatment plants to develop protective strategies for water safety and to eliminate waterborne parasites. © 2011 Springer-Verlag.

Li Y.,Harbin Medical University | Li Y.,Heilongjiang Provincial Key Laboratory for Infection and Immunity | Yang D.,Harbin Medical University | Wang J.-Y.,Harbin Medical University | And 15 more authors.
PLoS ONE | Year: 2014

The importance of the fourth variable (V4) region of the human immunodeficiency virus 1 (HIV-1) envelope glycoprotein (Env) in virus infection has not been well clarified, though the polymorphism of this region has been found to be associated with disease progression to acquired immunodeficiency syndrome (AIDS). In the present work, we focused on the correlation between HIV-1 gp120 V4 region polymorphism and the function of the region on virus entry, and the possible mechanisms for how the V4 region contributes to virus infectivity. Therefore, we analyzed the differences in V4 sequences along with coreceptor usage preference from CCR5 to CXCR4 and examined the importance of the amino acids within the V4 region for CCR5- and CXCR4-tropic virus entry. In addition, we determined the influence of the V4 amino acids on Env expression and gp160 processing intracellularly, as well as the amount of Env on the pseudovirus surface. The results indicated that V4 tended to have a shorter length, fewer potential N-linked glycosylation sites (PNGS), greater evolutionary distance, and a lower negative net charge when HIV-1 isolates switched from a coreceptor usage preference for CCR5 to CXCR4. The N- and C-terminals of the HIV-1 V4 region are highly conserved and critical to maintain virus entry ability, but only the mutation at position 417 in the context of ADA (a R5-tropic HIV-1 strain) resulted in the ability to utilize CXCR4. In addition, 390L, 391F, 414I, and 416L are critical to maintain gp160 processing and maturation. It is likely that the hydrophobic properties and the electrostatic surface potential of gp120, rather than the conformational structure, greatly contribute to this V4 functionality. The findings provide information to aid in the understanding of the functions of V4 in HIV-1 entry and offer a potential target to aid in the development of entry inhibitors. © 2014 Li et al.

Zheng Q.,Harbin Medical University | Zheng Q.,Heilongjiang Provincial Key Laboratory for Infection and Immunity | Han L.,Tianjin Medical University | Han L.,Tianjin Neurological Institute | And 27 more authors.
Neuro-Oncology | Year: 2014

Background. As a commonly mutated form of the epidermal growth factor receptor, EGFRvIII strongly promotes glioblastoma (GBM) tumor invasion and progression, but the mechanisms underlying this promotion are not fully understood. Methods. Through gene manipulation, we established EGFRvIII-, wild-type EGFR-, and vector-expressing GBM cells. We used cDNA microarrays, bioinformatics analysis, target-blocking migration and invasion assays, Western blotting, and an orthotopic U87MG GBM model to examine the phenotypic shifts and treatment effects of EGFRvIII expression in vitro and in vivo. Confocal imaging, co-immunoprecipitation, and siRNA assays detected the focal adhesion-associated complex and their relationships to the EGFRvIII/JAK2/STAT3 axis in GBM cells. Results. The activation of JAK2/STAT3 signaling is vital for promoting migration and invasion in EGFRvIII-GBM cells. AG490 or WP1066, the JAK2/STAT3 inhibitors, specifically destroyed EGFRvIII/JAK2/STAT3-related focal adhesions and depleted the activation of EGFR/Akt/FAK and JAK2/STAT3 signaling, thereby abolishing the ability of EGFRvIII-expressing GBM cells to migrate and invade. Furthermore, the RNAi silencing of JAK2 in EGFRvIII-expressing GBM cells significantly attenuated their ability to migrate and invade; however, as a result of a potential EGFRvIII-JAK2-STAT3 activation loop, neither EGFR nor STAT3 knockdown yielded the same effects. Moreover, AG490 or JAK2 gene knockdown greatly suppressed tumor invasion and progression in the U87MG-EGFRvIII orthotopic models. Conclusion. Taken together, our data demonstrate that JAK2/STAT3 signaling is essential for EGFRvIII-driven migration and invasion by promoting focal adhesion and stabilizing the EGFRvIII/JAK2/STAT3 axis. Targeting JAK2/STAT3 therapy, such as AG490, may have potential clinical implications for the tailored treatment of GBM patients bearing EGFRvIII-positive tumors. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved.

Yu H.-T.,Harbin Medical University | Tian D.,Harbin Medical University | Wang J.-Y.,Harbin Medical University | Wang J.-Y.,Heilongjiang Provincial Key Laboratory for Infection and Immunity | And 12 more authors.
PLoS ONE | Year: 2014

The CD4 binding site (CD4BS) of the HIV-1 envelope glycoprotein (Env) contains epitopes for broadly neutralizing antibody (nAb) and is the target for the vaccine development. However, the CD4BS core including residues 425-430 overlaps the B cell superantigen site and may be related to B cell exhaustion in HIV-1 infection. Furthermore, production of nAb and high-affinity plasma cells needs germinal center reaction and the help of T follicular helper (Tfh) cells. We believe that strengthening the ability of Env CD4BS in inducing Tfh response and decreasing the effects of the superantigen are the strategies for eliciting nAb and development of HIV-1 vaccine. We constructed a gp120 mutantW427S of an HIV-1 primary R5 strain and examined its ability in the elicitation of Ab and the production of Tfh by immunization of BALB/c mice. We found that the trimeric wild-type gp120 can induce more non-specific antibody-secreting plasma cells, higher serum IgG secretion, and more Tfh cells by splenocyte. The modified W427S gp120 elicits higher levels of specific binding antibodies as well as nAbs though it produces less Tfh cells. Furthermore, higher Tfh cell frequency does not correlate to the specific binding Abs or nAbs indicating that the wild-type gp120 induced some non-specific Tfh that did not contribute to the production of specific Abs. This gp120 mutant led to more memory Tfh production, especially, the effector memory Tfh cells. Taken together, W427S gp120 could induce higher level of specific binding and neutralizing Ab production that may be associated with the reduction of non-specific Tfh but strengthening of the memory Tfh. © 2014 Yu et al.

Teng X.,Harbin Medical University | Teng X.,Heilongjiang Provincial Key Laboratory for Infection and Immunity | Teng X.,Key Laboratory of Heilongjiang Province Education Bureau for Etiology | Liu J.-Y.,Harbin Medical University | And 22 more authors.
Journal of Viral Hepatitis | Year: 2011

Understanding the consequences of mutation in the tyrosine-methionine- aspartate-aspartate (YMDD) motif of hepatitis B virus (HBV) genome on replication is critical for treating chronic hepatitis B with lamivudine. Allele-specific gene silencing by RNAi (allele-specific RNAi: ASP-RNAi) is an advanced application of RNAi techniques. Use of this strategy as a means for specifically inhibiting an allele expression of interest suggested that it can specifically suppress the expression of alleles causing disease without inhibiting the expression of corresponding wild-type alleles. However, no studies have used ASP-RNAi to address the issue of HBV lamivudine resistance. In this study, we applied ASP-RNAi into two long-term eukaryotic cell lines of full-length HBV containing either lamivudine-resistant mutants (HBV-YIDD) or wild type (HBV-WT) which we generated in previously. The designed siRNAs were also used in this eukaryotic expression system together with lamivudine. ELISA and real-time PCR were performed to monitor virus-specific protein synthesis and viral DNA replication. The results showed that the base substitutions conferring marked ASP-RNAi appeared to be largely present in positions 1, 3, 6, 11, 12, 15 and 19 of the sense strand of siRNAs which were different from the most sensitive positions of this application in eukaryotes. In addition, siRNA-lamivudine combinations did not possess the prominent anti-HBV activity we expected because of some unknown mechanisms. These findings recapitulated many of the features of ASP-RNAi in hepadnaviruses which provided a new insight into the development of a potent strategy against HBV drug resistance. © 2011 Blackwell Publishing Ltd.

Teng X.,Harbin Medical University | Teng X.,Heilongjiang Provincial Key Laboratory for Infection and Immunity | Teng X.,Key Laboratory of Heilongjiang Province Education Bureau for Etiology | Xu W.-Z.,Harbin Medical University | And 20 more authors.
Journal of Virological Methods | Year: 2010

Drug-resistant hepatitis B virus (HBV) is a serious problem affecting antiviral therapy. In this study, two long-term eukaryotic cell lines with full-length HBV were constructed and contained either lamivudine-resistant mutants (HBV-YIDD) or wild-type virus (HBV-wt). High levels of intracellular viral DNA replication were observed continuously after transfecting the plasmids into HepG2 cells, and HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) were secreted into the cell culture supernatant. A series of experiments showed differential inhibition of HBV gene expression and replication by four specific siRNAs, according to the principles of allele-specific RNAi technology. The results showed that the designed siRNAs with a mismatch in the sixteenth nucleotide of the guide strands could effectively discriminate the HBV-YIDD mutants from the wild-type alleles, thus providing a new insight into the development of antiviral therapy with differing or complementary patterns characteristic of lamivudine-resistant HBV. © 2010 Elsevier B.V.

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