Yuanping Zhou

Chlamydia psittaci is variably associated with ocular adnexal MALT lymphoma in different geographical regions

Infectious agents play a critical role in MALT lymphoma development. Studies from Italy showed Chlamydia psittaci infection in 87% of ocular adnexal MALT lymphomas and complete or partial regression of the lymphoma after C. psittaci eradication in four of nine cases. However, C. psittaci was not demonstrated in ocular adnexal MALT lymphomas from the USA. This study was thus designed to investigate further the role of C. psittaci, and other infectious agents commonly associated with chronic eye disease, in the development of ocular adnexal MALT lymphoma. The presence of C. psittaci, C. trachomatis, C. pneumoniae, herpes simplex virus 1 and 2 (HSV1, HSV2), and adenovirus 8 and 19 (ADV8, ADV19) was assessed separately by polymerase chain reaction in 142 ocular adnexal MALT lymphomas, 53 non‐marginal zone lymphomas, and 51 ocular adnexal biopsies without a lymphoproliferative disorder (LPD), from six geographical regions. C. psittaci was detected at similar low frequencies in non‐LPD and non‐marginal zone lymphoma groups from different geographical regions (0–14%). Overall, the prevalence of C. psittaci was significantly higher in MALT lymphomas (22%) than in non‐LPD (10%, p = 0.042) and non‐marginal zone lymphoma cases (9%, p = 0.033). However, the prevalence of C. psittaci infection in MALT lymphoma showed marked variation among the six geographical regions examined, being most frequent in Germany (47%), followed by the East Coast of the USA (35%) and the Netherlands (29%), but relatively low in Italy (13%), the UK (12%), and Southern China (11%). No significant differences in the detection of C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8, and ADV19 were found between lymphomas and controls from different geographical regions. In conclusion, our results show that C. psittaci, but not C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8 or ADV19, is associated with ocular adnexal MALT lymphoma and that this association is variable in different geographical areas. Copyright

Role of hepatitis B virus genotypes and quantitative HBV DNA in metastasis and recurrence of hepatocellular carcinoma

Identification of risk factors for recurrence and metastasis of HCC is important for the prognosis of HCC surveillance in chronic HBV infection. In this article, 125 HCC patients recruited were followed up prospectively for tumor metastasis and recurrence for a median of 104 (10–130) weeks. HBV DNA level was detected by LightCycler‐based real‐time fluorescence quantitative polymerase chain reaction‐restriction system. HBV genotypes were determined by using PCR restriction‐fragment length polymorphism. BCP and PC mutations were performed by PCR and direct sequencing of amplified products. Among 125 HCC patients, 19 patients were excluded because of the lack of follow‐up data and the remaining 106 patients were followed up of 2 years and entered into analysis. Sixty‐nine patients had tumor metastasis or recurrence during the follow‐up and the cumulative probability of HCC metastasis or recurrence was 65.1%. On multivariate analysis, genotype C and HBV DNA level were the risk factors for HCC recurrence or metastasis. The incidence of recurrence or metastasis increased with baseline HBV DNA level in a dose‐response relationship ranging from 22% for HBV DNA level of less than 3 log10 copies/ml to 80% for HBV DNA level of 5 log10 copies/ml or greater (P = 0.012). Fifty‐seven (74.0%) and 12 (41.4%) patients had metastasis or recurrence in patients with genotype C and B, respectively. The adjusted OR of recurrence or metastasis for genotype C compared with genotype B was 9.755 (P = 0.009). In conclusion, elevated HBV DNA level and genotype C are strong risk predictors of HCC metastasis or recurrence. J. Med. Virol. 80:591–597, 2008.

Characterization of severe hand, foot, and mouth disease in Shenzhen, China, 2009–2013

Hand, foot, and mouth disease (HFMD) is caused by human enteroviruses, especially by enterovirus 71 (EV71) and coxsackievirus A16 (CA16). Patients infected with different enteroviruses show varied clinical symptoms. The aim of this study was to determine whether the etiological spectrum of mild and severe HFMD changed, and the association between pathogens and clinical features. From 2009 to 2013, a total of 2,299 stool or rectal specimens were collected with corresponding patient data. A dynamic view of the etiological spectrum of mild and severe HFMD in Shenzhen city of China was provided. EV71 accounted for the majority proportion of severe HFMD cases and fatalities during 2009–2013. CA16 and EV71 were gradually replaced by coxsackievirus A6 (CA6) as the most common serotype for mild HFMD since 2010. Myoclonic jerk and vomiting were the most frequent severe symptoms. Nervous system complications, including aseptic encephalitis and aseptic meningitis were observed mainly in patients infected by EV71. Among EV71, CA16, CA6, and CA10 infection, fever and pharyngalgia were more likely to develop, vesicles on the hand, foot, elbow, knee and buttock were less likely to develop in patients infected with CA10. Vesicles on the mouth more frequently occurred in the patients with CA6, but less in the patient with EV71. Associations between diverse enterovirus serotypes and various clinical features were discovered in the present study, which may offer further insight into early detection, diagnosis and treatment of HFMD. J. Med. Virol. 87:1471–1479, 2015.

Serum HBsAg changes in HBeAg positive chronic hepatitis B patients with continuous viral load reductions during treatment with adefovir or peg-interferon-α-2a.

Hepatitis B surface antigen (HBsAg) loss under antiviral therapy is rare in chronic hepatitis B patients and the dynamics of serum HBsAg in these patients are not available. The changes in serum HBsAg following treatment with adefovir (n=31) or peg-interferon-alpha-2a (n=23) were studied in hepatitis B e-antigen (HBeAg) positive chronic hepatitis B patients. Abbott Architect HBsAg assay was used to quantify serum HBsAg. HBsAg levels were significantly decreased during the first 12 weeks of treatment with median change of -397.0 IU/ml and -555.4 IU/ml, respectively for adefovir and peg-interferon-alpha-2a (p=0.005 and 0.001, respectively). Beyond 12 weeks, no further significant HBsAg reductions were found even in patients with sustained viral replication inhibition in either group. Three distinct patterns of HBsAg changes were observed in most patients in both treatment groups: biphasic pattern (rapid HBsAg reduction from baseline to week 12); assurgent pattern (higher HBsAg level at week 12 than at baseline); and wavy pattern (HBsAg reduction from baseline to week 12, followed by relapse at week 24 or week 28). These results might offer insights into the possible mechanism(s) underlying the unusual occurrences of HBsAg loss under antiviral therapy.

GTPase activity is not essential for the interferon-inducible MxA protein to inhibit the replication of hepatitis B virus

Multiple studies have established that GTPase activity is critical for MxA to act against RNA viruses. Recently, it was shown that MxA can also restrict the replication of hepatitis B virus (HBV), a DNA virus, but the requirements for GTPase activity in inhibition of HBV by MxA remain unknown. Here, we report that GTPase-defective mutants (K83A, T103A, and L612K) can downregulate extracellullar HBsAg and HBeAg and reduce the expression of extra- and intracellular HBV DNA in HepG2 cells to levels similar to that achieved by wild-type MxA. Furthermore, TMxA and T103, two nuclear forms of wild-type MxA and a GTPase-defective mutant (T103A) could only slightly decrease the expression of extra- and intracellular HBV DNA in HepG2 cells. In conclusion, GTPase activity is not essential for MxA protein to inhibit HBV replication, and MxA may have only a minimal effect on the replicative cycle of HBV in the nucleus.

Spatiotemporal Characterizations of Dengue Virus in Mainland China: Insights into the Whole Genome from 1978 to 2011

Temporal-Spatial of dengue virus (DENV) analyses have been performed in previous epidemiological studies in mainland China, but few studies have examined the whole genome of the DENV. Herein, 40 whole genome sequences of DENVs isolated from mainland China were downloaded from GenBank. Phylogenetic analyses and evolutionary distances of the dengue serotypes 1 and 2 were calculated using 14 maximum likelihood trees created from individual genes and whole genome. Amino acid variations were also analyzed in the 40 sequences that included dengue serotypes 1, 2, 3 and 4, and they were grouped according to temporal and spatial differences. The results showed that none of the phylogenetic trees created from each individual gene were similar to the trees created using the complete genome and the evolutionary distances were variable with each individual gene. The number of amino acid variations was significantly different (p = 0.015) between DENV-1 and DENV-2 after 2001; seven mutations, the N290D, L402F and A473T mutations in the E gene region and the R101K, G105R, D340E and L349M mutations in the NS1 region of DENV-1, had significant substitutions, compared to the amino acids of DENV-2. Based on the spatial distribution using Guangzhou, including Foshan, as the indigenous area and the other regions as expanding areas, significant differences in the number of amino acid variations in the NS3 (p = 0.03) and NS1 (p = 0.024) regions and the NS2B (p = 0.016) and NS3 (p = 0.042) regions were found in DENV-1 and DENV-2. Recombination analysis showed no inter-serotype recombination events between the DENV-1 and DENV-2, while six and seven breakpoints were found in DENV-1 and DENV-2. Conclusively, the individual genes might not be suitable to analyze the evolution and selection pressure isolated in mainland China; the mutations in the amino acid residues in the E, NS1 and NS3 regions may play important roles in DENV-1 and DENV-2 epidemics.

NS1-based tests with diagnostic utility for confirming dengue infection: a meta-analysis

OBJECTIVES Non-structural protein 1 (NS1)-based tests may offer a larger window of opportunity for dengue diagnosis and could constitute a very useful diagnostic tool. The aim of this study was to establish the overall accuracy of NS1-based tests for diagnosing dengue infection. METHODS A meta-analysis was conducted including 18 studies published up to October 1, 2012 identified using PubMed, ISI Web of Science, Google Scholar, and the Chinese National Knowledge Infrastructure (CNKI) database. RESULTS For the single NS1-based tests - ELISA (Panbio Dengue Early ELISA Kit, Dengue NS1 Ag ELISA Kit, and Platelia Dengue NS1 Ag-ELISA Kit) and immunochromatography (Dengue NS1 Ag STRIP Kit and SD BIOLINE Dengue Duo Strip Kit) - the summarized sensitivities and specificities were 67% (95% confidence interval (CI) 59-74%) and 99% (95% CI 97-99%), and 71% (95% CI 61-79%) and 99% (95% CI 98-100%), respectively. The hierarchical summary receiver operating characteristics (HSROCs) were 0.92 and 0.96, respectively. For NS1 combined with an anti-dengue-specific IgM test, the summarized sensitivity, specificity, and HSROC were 83% (95% CI 68-92%), 86% (95% CI 79-91%), and 0.91 (95% CI 0.89-0.93), respectively. The accuracy for serotypes was 50.0-90.9% for DENV-1, 38.5-85.7% for DENV-2, 46.7-91.3% for DENV-3, and 21.7-87.0% for DENV-4. CONCLUSIONS These results support the use of single NS1-based tests; they have good diagnostic utility for confirming dengue and for distinguishing serotypes DENV-1 and 3 from DENV-2 and 4, while they can be used as a screening tool when combined with an IgM test. Moreover, the Dengue NS1 Ag STRIP Kit appears to be the best for confirming and serotyping dengue infection.

Predicting sustained viral response to hepatitis C using a rapid and simple IL28B rs8099917 genotyping assay

Recent studies showed that two single nucleotide polymorphisms (SNPs) (rs12979860 and rs8099917) near the gene IL28B coding for IFNλ3 were associated with the antiviral treatment response of the combination therapy of pegIFN plus RBV. We established the use of tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) for detecting IL28B rs8099917 genotype (T>G) in 56 Chinese chronic hepatitis C patients infected with Hepatitis C Virus (HCV) genotype 1. The new assay showed 98.2% specificity, and was confirmed by direct sequencing. Among the 56 samples, TT genotype and TG genotype accounted for 80.4% (45/56) and 19.6% (11/56), respectively. GG genotype was not found. The proportion of responders in TT group was higher than that in TG group (68.9% vs. 27.3%, p=0.029). For HCV clinical decision-making, using the new assay, rs8099917 genotyping could provide similar information to rs12979860 genotyping due to a strong association between the two SNPs in Chinese patients. The assay system in this study can be implemented using basic laboratory equipments, making it convenient for clinical and research purposes.

Gastroenteritis Outbreaks Associated with the Emergence of the New GII.4 Sydney Norovirus Variant during the Epidemic of 2012/13 in Shenzhen City, China.

Noroviruses (NoVs) are the leading cause of gastroenteritis outbreaks in humans worldwide. Since late 2012, a new GII.4 variant Sydney 2012 has caused a significant increase in NoV epidemics in several countries. From November of 2012 to January of 2013, three gastroenteritis outbreaks occurred in two social welfare homes (Outbreaks A and B) and a factory (Outbreak C) in Shenzhen city of China. Feces and swabs were collected for laboratory tests for causative agents. While no bacterial pathogen was identified, all three outbreaks were caused by NoVs with detection rates of 26.2% (16/61) at Outbreak A, 35.2% (38/108) at Outbreak B), and 59.3% (16/27) at Outbreaks C. For Outbreak B, 25 of the 29 symptomatic individuals (86.2%) and 13 of the 79 asymptomatic individuals (16.5%) were found NoV-positive. For Outbreak C, an asymptomatic food handler was NoV-positive. All thirteen NoV sequences from the three outbreaks were classified into genogroup II and genotype 4 (GII.4), which we identified to be the GII.4 Sydney 2012 variant. The genome of two isolates from Outbreaks A and B were recombinant with the opening reading frame (ORF) 1 of GII.4 Osaka 2007 and ORF2 and 3 of the GII.4 New Orleans. Our study indicated that the GII.4 Sydney 2012 variant emerged and caused the outbreaks in China.

Hepatitis C virus amino acid sequence diversity correlates with the outcome of combined interferon/ribavirin therapy in Chinese patients with chronic hepatitis C

Evidence has shown that the p7, NS2 and NS3 genes affect the outcome of pegylated-IFN-α/ribavirin (PEG-IFN/RBV) combination therapy in different populations with HCV infections. Here, we test the hypothesis that diversity in the p7, NS2 and NS3 genes influences the probability of obtaining either a sustained (SVR) or non-sustained (non-SVR) viral response in Chinese patients with genotype 1b chronic hepatitis C. There were significantly more unique variations in the p7, NS2 and NS3 genes in the sequences from SVR than non-SVR patients. Inter-patient variations related to treatment outcome in NS3 were concentrated in the protease domain. There were no significant differences in the frequency of variations in the core, E1 and E2 proteins between the groups. In conclusion, increased amino acid sequence diversity in the p7, NS2 and NS3 genes is associated with an SVR to PEG-IFN/RBV therapy in Chinese patients with genotype 1b chronic hepatitis C.