PDF(Pubmed)
Abstract：
BACKGROUND: HIV elite controllers represent a rare subset of persons living with HIV, able to spontaneously control viral replication without antiviral therapy. HLA-B∗57 and HLA-B∗27 alleles are associated to efficient polyfunctional CD8+ T-cell response and are overrepresented in elite controllers but these alleles alone incompletely explain spontaneous HIV replication control in these subjects. Further mechanisms involved in innate and adaptive immune response and host genetics may contribute to this control. In this context, the homeostatic iron regulator (HFE) gene encodes a major histocompatibility complex-class-I-like molecule involved in both innate immunity, acting also through autophagy regulation, and iron homeostasis, strictly related to immune functions and susceptibility to infections.
METHODS: Homozygousity for the p.His63Asp (H63D) variant in the HFE gene was identified in an 80-year-old HIV-infected woman with spontaneous control of viral replication.
METHODS: HIV-1 RNA was undetectable in patient\'s serum with a routine assay and an ultra-sensitive assay (<1 copy/mL) during the 30 years follow-up. CD4+ and CD8+ T cell counts were stable and normal during all this period.
METHODS: The patient had a history of absence of any physical ailment and no antiviral therapy has been prescribed during the 30 years of follow-up. The subject did not harbor HLA-B∗57 and HLA-B∗27 alleles. HFE gene was sequenced by Sanger, as part of a larger study on a cohort of HIV infected patients, aged >65 years and screened for polymorphisms in genes belonging to several pathways involved in neuroinflammation.
RESULTS: The woman had CD4+ and CD8+ T cell normal values and spontaneously controlled serum HIV-1 RNA levels for 30 years.
CONCLUSIONS: We assume that the interplay between the HFE H63D variant in homozygosity and innate immunity, perhaps through autophagy regulation, could play a role in HIV-1 replication control in our patient. This hypothesis needs to be explored in in vitro and in vivo studies. Understanding mechanisms involved in spontaneous control of HIV-1 replication remains indeed a challenge due to its possible implications for HIV cure research.
METHODS: Homozygousity for the p.His63Asp (H63D) variant in the HFE gene was identified in an 80-year-old HIV-infected woman with spontaneous control of viral replication.
METHODS: HIV-1 RNA was undetectable in patient\'s serum with a routine assay and an ultra-sensitive assay (<1 copy/mL) during the 30 years follow-up. CD4+ and CD8+ T cell counts were stable and normal during all this period.
METHODS: The patient had a history of absence of any physical ailment and no antiviral therapy has been prescribed during the 30 years of follow-up. The subject did not harbor HLA-B∗57 and HLA-B∗27 alleles. HFE gene was sequenced by Sanger, as part of a larger study on a cohort of HIV infected patients, aged >65 years and screened for polymorphisms in genes belonging to several pathways involved in neuroinflammation.
RESULTS: The woman had CD4+ and CD8+ T cell normal values and spontaneously controlled serum HIV-1 RNA levels for 30 years.
CONCLUSIONS: We assume that the interplay between the HFE H63D variant in homozygosity and innate immunity, perhaps through autophagy regulation, could play a role in HIV-1 replication control in our patient. This hypothesis needs to be explored in in vitro and in vivo studies. Understanding mechanisms involved in spontaneous control of HIV-1 replication remains indeed a challenge due to its possible implications for HIV cure research.
摘要：
背景：HIV精英控制者代表了一个罕见的HIV感染者子集，能够在没有抗病毒治疗的情况下自发控制病毒复制。HLA-B*57和HLA-B*27个等位基因与有效的多功能CD8T细胞反应相关，并且在精英控制者中被过度代表，但这些等位基因不能完全解释这些受试者的自发性HIV复制控制。先天和适应性免疫应答和宿主遗传学中涉及的其他机制可能有助于这种控制。在这种情况下，稳态铁调节剂（HFE）基因编码一个主要的组织相容性复杂的I类分子参与两种先天免疫，也通过自噬调节，和铁稳态，与免疫功能和感染易感性严格相关。
方法：在一名80岁感染HIV的女性中鉴定了HFE基因中p.His63Asp（H63D）变体的纯合性，该女性自发控制了病毒复制。
方法：在30年的随访中，常规检测和超敏感检测（<1拷贝/mL）在患者血清中检测不到HIV-1RNA。CD4+和CD8+T细胞计数在这期间是稳定和正常的。
方法：患者有没有任何身体疾病的病史，在30年的随访中没有规定抗病毒治疗。受试者未携带HLA-B*57和HLA-B*27等位基因。由Sanger对HFE基因进行测序,作为对HIV感染患者队列的更大研究的一部分，年龄>65岁，并筛选了涉及神经炎症的几种途径的基因多态性。
结果：该女性具有30年的CD4+和CD8+T细胞正常值和自发控制的血清HIV-1RNA水平。
结论：我们假设HFEH63D变体在纯合性和先天免疫之间的相互作用，也许通过自噬调节，可以在我们患者的HIV-1复制控制中发挥作用。这一假设需要在体外和体内研究中进行探索。理解HIV-1复制的自发控制机制仍然是一个挑战，因为它可能对HIV治愈研究产生影响。
方法：在一名80岁感染HIV的女性中鉴定了HFE基因中p.His63Asp（H63D）变体的纯合性，该女性自发控制了病毒复制。
方法：在30年的随访中，常规检测和超敏感检测（<1拷贝/mL）在患者血清中检测不到HIV-1RNA。CD4+和CD8+T细胞计数在这期间是稳定和正常的。
方法：患者有没有任何身体疾病的病史，在30年的随访中没有规定抗病毒治疗。受试者未携带HLA-B*57和HLA-B*27等位基因。由Sanger对HFE基因进行测序,作为对HIV感染患者队列的更大研究的一部分，年龄>65岁，并筛选了涉及神经炎症的几种途径的基因多态性。
结果：该女性具有30年的CD4+和CD8+T细胞正常值和自发控制的血清HIV-1RNA水平。
结论：我们假设HFEH63D变体在纯合性和先天免疫之间的相互作用，也许通过自噬调节，可以在我们患者的HIV-1复制控制中发挥作用。这一假设需要在体外和体内研究中进行探索。理解HIV-1复制的自发控制机制仍然是一个挑战，因为它可能对HIV治愈研究产生影响。
