title: Polymorphisms in the PE35 and PPE68 antigens in Mycobacterium tuberculosis strains may affect strain virulence and reflect ongoing immune evasion.
abstract: Previous studies have demonstrated that the Pro‑Glu/Pro‑Pro‑Glu (PE/PPE) genes in strains of Mycobacterium tuberculosis exhibit high sequence variation and may be involved in antigenic variation and immune evasion. Region of Difference 1 (RD1), encoding genes from Rv3871 to Rv3879, was observed to be lost during the original derivation of Bacillus Calmette‑Guérin between 1908 and 1921. It has been previously demonstrated that two PE/PPE proteins, PE35 (Rv3872) and PPE68 (Rv3873), are encoded by RD1 and exhibit immunodominance. To explore the genetic diversity of PE35 and PPE68, and to evaluate the impact of sequence variation on the immune recognition of these proteins, 161 clinical M. tuberculosis strains were selected from China and comparative sequence analysis of PE35 and PPE68 was performed. The results indicated that polymorphisms in PE35 and PPE68 may lead to alterations in the function of these proteins, which may potentially affect strain virulence. In addition, the human T‑cell epitopes of PE35 and PPE68 were highly variable, suggesting that the two antigens may be involved in diversifying selection to evade host immunity. The prevalence of strains with PE35 mutations in the non‑Beijing family was significantly greater compared with the Beijing family, indicating that Beijing strains may be more conservative than non‑Beijing strains in this gene.
authors.affiliation: Department of Tuberculosis, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Tuberculosis, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China.
authors.forename: Jianhao
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Tuberculosis, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China.
authors.forename: Haican
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Tuberculosis, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China.
authors.forename: Guilian
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Tuberculosis, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Tuberculosis, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Tuberculosis, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Tuberculosis, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China.
authors.forename: Machao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Tuberculosis, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institute for Infectious Disease Prevention and Control, Beijing Center for Disease Prevention and Control, Beijing 100013, P.R. China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Dou
authors.affiliation: Department of Tuberculosis, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China.
authors.forename: Kanglin
authors.initials: K
authors.lastname: Wan
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics*; D002681:China; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; C000611212:PE35 antigen, Mycobacterium tuberculosis; C528814:PPE68 protein, Mycobacterium tuberculosis