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10 Delta32突变
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首篇探讨由于缺乏CCR5因而对HIV的感染产生抵抗性的论文:“Homozygous defect in HIV-1 co-receptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection,” Cell 86(1996).
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大部分具有Delta32(Δ32)的个体仍能过着健康的生活,但有少数研究指出缺乏CCR5基因的个体为感染西尼罗病毒的高风险群体。这些研究结果彼此并不一致。我们尚无法确定CCR5的缺失将引发的各种结果。其余研究则指出,Delta32突变对于部分疾病可提供保护,例如脑型疟疾等。各方面研究可参见:“CCR5 deficiency increases risk of symptomatic West Nile virus infection,” Journal of Experimental Medicine 203(2006);“CCR5 deficiency is a risk factor for early clinical manifestations of West Nile virus infection but not for viral transmission,” Journal of Infectious Diseases 201(2010);“Role of chemokines polymorphisms in diseases,” Immunology Letters 145(2012).
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绝大多数感染性病毒都会通过CCR5受体进入细胞,详见何大一的论文:“Genotypic and phenotypic characterization of HIV-1 patients with primary infection,” Science 261(1993).
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不论是通过性行为,还是静脉注射,或母体至胎儿等途径,病毒都是通过CCR5进行传染的:“Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual,parenteral,and vertical transmission,” Journal of Clinical Investigation 94(1994).
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CCR5的Delta32突变,在西欧人中相当常见,相关报告参见:“Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene,” Nature 382(1996);“The geographic spread of the CCR5 Delta32 HIV-resistance allele,” PLoS Biology 3(2005).
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许特尔在医学院图书馆中所读到的,同时也是第一篇描述Delta32突变与HIV之关联的论文:“Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene,” Nature 6593(1996).
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11 呼叫所有非凡控制者
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A Song in the Night:A Memoir of Resilience by Bob Massie(Doubleday,2012).
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布鲁斯·沃克与鲍勃·马西之间的关联,以及前者对于这些非凡控制者世代的研究进程,其细节来自个人访谈。其他细节以及“我那时一定大声地惊叹了一声”这句话,摘录自:“Secrets of the HIV controllers,” Scientific American 307(2012).
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关于囊肿性纤维化的基因治疗,详见:“Cystic fibrosis transmembrane conductance regulator protein repair as a therapeutic strategy in cystic fibrosis,” Current Opinion in Pulmonary Medicine 16(2010).
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关于帕金森病的基因治疗,详见:“Safety and tolerability of gene therapy with an adeno-associated virus(AAV)borne GAD gene for Parkinson’s disease:an open label,phase I trial,” Lancet 369(2007).
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关于乙型地中海贫血的基因治疗,详见:“Beta-thalassemia treatment succeeds,with a caveat,” Science 326(2009).
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关于遗传性失明的基因治疗,详见:Maguire AM,High KA,Auricchio A,Wright JF,Pierce EA,Testa F,Mingozzi F,Bennicelli JL,Ying GS,Rossi S,et al.,“Age-dependent effects of RPE65 gene therapy for Leber’s congenital amaurosis:a phase 1 dose-escalation trial,” Lancet 374(9701):1597-605;2009.
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关于杰西·格尔辛格于1999年在接受基因治疗后死亡及其对研究引起的冲击,详见:“Gene therapy death prompts review of adenovirus vector,” Science 286(1999).
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关于流行病学及HIV控制者的描述,详见:“Prevalence and comparative characteristics of long-term nonprogressors and HIV controller patients in the French Hospital Database on HIV,” AIDS 23(2009).
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关于淋巴细胞组织大量表现CCR5的现象,详见:“Expression of the chemokine receptors CCR4,CCR5,and CXCR3 by human tissue-infiltrating lymphocytes,” American Journal of Pathology 160(2002).
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关于肠道在HIV急性感染期的重要性的讨论,详见:“Immunopathogenesis of acute AIDS virus infection,” Current Opinion in Immunology 18(2006).
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关于人类白细胞抗原分型与HIV的概论,详见:“HIV and HLA class I:an evolving relationship,” Immunity 37(2012).
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关于HIV控制者的身上常可发现HLA对偶基因B*27和B*57,详见:“HLA alleles associated with delayed progression to AIDS contribute strongly to the initial CD8+ T-cell response against HIV-1,” PLoS Medicine 3(2006).
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关于猴子版的HIV非凡控制,Mamu-A*01对偶基因的出现能够保护灵长类免于SIV的感染,详见:“Mamu-A*01 allele-mediated attenuation of disease progression in simian-human immunodeficiency virus infection,” Journal of Virology 76(2002).
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关于控制着HIV,且位于HLA-B基因沟中的特定氨基酸,详见:“The major genetic determinants of HIV-1 control affect HLA class I peptide presentation,” Science 330(2010).
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关于HLA-B*57与银屑病之关联的探讨,详见:“HLA-B57 is significantly associated with psoriasis in Northeast Romania,” Roumanian Archives of Microbiology and Immunology 61(2002).
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12 躲藏起来的疗法
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关于医学院毕业生担任家庭医生的比例,详见:“Entry of US medical school graduates into family medicine residencies,” Family Medicine 44(2012).
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