[Evaluation of immune responses and related patho-inflammatory reactions of a candidate inactivated EV71 vaccine in neonatal monkeys].

OBJECTIVE: To evaluate the safety of enterovirus type 71 (EV71) inactivated vaccine (human diploid derived) for infection prevention in an animal model by investigating the immune responses and related patho-inflammatory reactions. METHODS: In the neonatal monkey model for EV71 vaccine protection, vaccinated group (n = 4) and unvaccinated group (n = 4) were attacked with live virus at the same time, the parameters of clinical observations, antibodies and inflammatory factors in peripheral blood and cerebrospinal fluid (CSF) were detected. And the pathological changes in major organs were used to determine the patho-inflammatory reactions during the immune responses elicited by vaccination. RESULTS: The neutralizing antibodies of vaccine group reach to 1:32. There was no obvious changes of inflammatory factors in peripheral blood and CSF of monkeys challenged or unchallenged by live virus. In peripheral blood of unvaccinated group, the level of basophilic granulocyte higher 4 - 5 times than normal level and the interferon-γ (IFN-γ) showed obvious increase. Live virus infected after 7 days, the interleukin-6 (IL-6) and IFN-γ in peripheral blood of unvaccinated group (18.5, 12.7 pg/ml) were higher than vaccinated group (10.2, 7.6 pg/ml). Furthermore, the IL-6 in CSF (102.0 pg/ml) had 4 - 5 times increased than vaccinated group (12.4 pg/ml) at 7 days after virus exposure. Meanwhile, the pathological analysis revealed that no obvious changes were detected in CNS and other organs of vaccinated monkeys challenged with live virus. However, the pathological damages induced by virus infection could be determined in the unvaccinated control monkeys, including neuronal damage, massive cellular infiltration associated with pulmonary edema/hemorrhage and pulmonary/bronchial damage due to an infiltration of inflammatory cells. CONCLUSION: Capable of inducing an immune response, the EV71 inactivated vaccine offers protection to neonatal rhesus monkeys against the attacks of live virus. Based on the results of no patho-inflammatory reaction and pathological damage after viral infection in vaccinated animals, the excellent safety of this vaccine may be confirmed in neonatal monkey.

[Biological characters of a coxsackievirus B3 variant strain isolated from a hand-foot-mouth disease patient with severe clinical symptoms].

OBJECTIVE: To analyze the genetic and biological characters of a new isolate of coxsackievirus B3 (CoxB3), i.e. FY-19 strain, and investigate its mechanistic role in causing different clinical symptoms of hand-foot-mouth disease (HFMD). METHODS: FY-19 strain, isolated from a patient with severe clinical symptoms from Fuyang, China in 2008, was identified by the serological parameters via the Lim Benyesh-Melnick (LBM) antiserum pools. Its genotype was further characterized by sequencing the whole genome. And its biological characters were also examined by proliferation kinetic and pathogenetic analysis. RESULTS: FY-19 strain was identified as CoxB3 showing 23.0%, 16.5% and 32.1% difference with Nancy strain in 3'-, 5'-noncoding and coding regions respectively. FY-19 also showed a high homology with other HFMD-related CoxB3 isolates in China. But its homology with non-HFMD-related CoxB3 isolates was lower (13.5% and 25.0% difference in 3'-NCR and coding region respectively). The viral replication kinetic analysis suggested that the FY-19 proliferation increased rapidly and peaked at 14 hours post-infection. In pathological analysis, FY-19 strain induced mortal pathology in sucking mice. CONCLUSION: Differences in genetic and biological characters exist between FY-19 and Nancy strains. Further analysis on the pathogenesis of this variant may aid in elucidating the mechanisms of HFMD.

Transcriptional regulation by HSV-1 induced HTRP via acetylation system.

The protein HTRP (human transcription regulator protein) is encoded by the differential gene htrp and induced by Herpes simplex virus type 1 (HSV-1) infection in KMB-17 cells. HTRP was found to interact with SAP30 (mSin3A Association Protein), one of the components of co-repressor complex mSin3A, which is part of the deacetylation transfer enzyme HDAC. To reveal the biological significance of the interaction between HTRP and SAP30, real- time PCR and a dual-luciferase detecting system was used. The results indicate that HTRP could inhibit the transcription of a viral promoter, whose interaction with SAP30 synergistically affects transcriptional inhibition of the viral genes, and is related to HDAC enzyme activity. ChIP experiments demonstrate that HTRP could promote HDAC activity by increasing the deacetylation level of lysine 14 and lysine 9 in histone H3.