Bai Xue-fan

Prediction and Identification-Based Prediction of Chinese Hepatitis C Viral-Specific Cytotoxic T Lymphocyte Epitopes

Cytotoxic T lymphocytes (CTLs) play a critical role in the host immune response to infection by the Hepatitis C Virus (HCV). In the current study, a number of HCV CTL epitopes that represent the HLA polymorphisms found in the majority of Chinese people were predicted based on genomic and bioinformatic approaches. The predicted epitopes were evaluated for validity by examining the peptide‐binding affinity for MHC class I molecules, the stability of peptide–MHC complexes, and frequencies of IFN γ‐positive T cells. Among the predicted epitope peptides, HLA‐A2 restricted epitopes [NS4B (1793–1801) SMMAFSAAL] and HLA‐B7 restricted epitopes [P7 (774–782) AAWYIKGRL] were able to induce high frequencies of IFN γ‐producing T cells, and the specific CTLs for other epitopes were not detected in peripheral blood lymphocytes from patients with HCV. Moreover, NS4B (1793–1801) exhibited high binding affinity for HLA‐A2 molecules, and its stability of peptide–MHC class I complexes was sufficient, indicating that the high binding affinity for MHC class I molecules is an important factor for immunogenicity. Primary analyses of the immunogenicity of predicted epitopes, such as in the current study, will contribute to the future design of an efficient vaccine that will be able to induce vigorous, sustainable, and broad HCV‐specific CTL responses for the Chinese population. J. Med. Virol. 83:1315–1320, 2011.

Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome

Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon-induced transmembrane proteins (IFITMs) as an interferon-stimulated gene family. However, the role of IFITMs in HTNV infection is unclear. In this study, we observed that IFITM3 single nucleotide polymorphisms (SNP) rs12252 C allele and CC genotype associated with the disease severity and HTNV load in the plasma of HFRS patients. In vitro experiments showed that the truncated protein produced by the rs12252 C allele exhibited an impaired anti-HTNV activity. We also proved that IFITM3 was able to inhibit HTNV infection in both HUVEC and A549 cells by overexpression and RNAi assays, likely via a mechanism of inhibiting virus entry demonstrated by binding and entry assay. Localization of IFITM3 in late endosomes was also observed. In addition, we demonstrated that the transcription of IFITM3 is negatively regulated by an lncRNA negative regulator of interferon response (NRIR). Taken together, we conclude that IFITM3, negatively regulated by NRIR, inhibits HTNV infection, and its SNP rs12252 correlates with the plasma HTNV load and the disease severity of patients with HFRS.