Case report: mechanisms of HIV elite control in two African women.
Case report: mechanisms of HIV elite control in two African women.
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病例报告：两名非洲妇女的艾滋病毒精英控制机制。
DOI：
10.1186/s12879-018-2961-8
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发表时间：
2018-01-25
影响因子：
3.7
通讯作者：
Burgers WA
中科院分区：
文献类型：
--
作者：
Moosa Y;Tanko RF;Ramsuran V;Singh R;Madzivhandila M;Yende-Zuma N;Abrahams MR;Selhorst P;Gounder K;Moore PL;Williamson C;Abdool Karim SS;Garrett NJ;Burgers WA
大多数艾滋病毒感染者需要抗逆转录病毒治疗（ART）来控制病毒复制，但很少有艾滋病毒控制者在没有治疗的情况下自发和持久地控制艾滋病毒。了解是什么介导了这些个体的病毒控制，为我们提供了对免疫机制的深入了解，这些免疫机制可能对诱导HIV疫苗或功能性治愈非常重要。迄今为止，很少有非洲精英控制器从高发病率设置已被描述。我们从南非夸祖鲁纳塔尔的CAPRISA 002队列HIV-1 C亚型感染妇女中确定了病毒学控制者，其中两人（1%）是精英控制者。我们详细研究了这两个精英HIV控制者的遗传、临床、免疫学和病毒学特征，以确定它们是否表现出与文献中报道的精英控制者相似的推定病毒控制特征。在本病例报告中，我们介绍了两名非洲妇女7年以上的艾滋病毒感染的临床特征，CD 4 + T细胞和病毒载量轨迹。HIV感染后10个月，精英控制者1（EC 1）和精英控制者2（EC2）在6周后病毒载量变得不可检测，并且在没有ART的情况下，在随访期间仍然不可检测。两个精英控制者表达先前与较慢的疾病进展相关的多种HLA I类和II类单倍型（HLA-A*74：01，HLA-B*44：03，HLA-B*81：01，HLA-B*57：03，HLA-DRB 1 *13）。健身试验表明，这两名妇女感染复制能力的病毒，都表达较高的mRNA水平的p21，宿主限制因子与病毒控制。使用流式细胞术检查HIV特异性T细胞应答。EC 1安装高频率的HIV特异性CD 8 + T细胞应答，包括B*81：01限制性Gag TL 9应答。不寻常的是，EC2有感染前HIV特异性CD 4 + T细胞应答的证据。我们确定了精英控制者的一些典型特征，包括高强度的HIV特异性反应和有益的HLA。此外，我们在一名精英控制者中发现了感染前HIV特异性免疫的非典型发现，这可能有助于非常早期的病毒控制。这份报告强调了在高发病率环境中研究艾滋病毒控制者的重要性。本文的在线版本（10.1186/s12879-018-2961-8）包含补充材料，可供授权用户使用。
The majority of people living with HIV require antiretroviral therapy (ART) for controlling viral replication, however there are rare HIV controllers who spontaneously and durably control HIV in the absence of treatment. Understanding what mediates viral control in these individuals has provided us with insights into the immune mechanisms that may be important to induce for a vaccine or functional cure for HIV. To date, few African elite controllers from high incidence settings have been described. We identified virological controllers from the CAPRISA 002 cohort of HIV-1 subtype C infected women in KwaZulu Natal, South Africa, two (1%) of whom were elite controllers. We examined the genetic, clinical, immunological and virological characteristics of these two elite HIV controllers in detail, to determine whether they exhibit features of putative viral control similar to those described for elite controllers reported in the literature. In this case report, we present clinical features, CD4+ T cell and viral load trajectories for two African women over 7 years of HIV infection. Viral load became undetectable 10 months after HIV infection in Elite Controller 1 (EC1), and after 6 weeks in Elite Controller 2 (EC2), and remained undetectable for the duration of follow-up, in the absence of ART. Both elite controllers expressed multiple HLA Class I and II haplotypes previously associated with slower disease progression (HLA-A*74:01, HLA-B*44:03, HLA-B*81:01, HLA-B*57:03, HLA-DRB1*13). Fitness assays revealed that both women were infected with replication competent viruses, and both expressed higher mRNA levels of p21, a host restriction factor associated with viral control. HIV-specific T cell responses were examined using flow cytometry. EC1 mounted high frequency HIV-specific CD8+ T cell responses, including a B*81:01-restricted Gag TL9 response. Unusually, EC2 had evidence of pre-infection HIV-specific CD4+ T cell responses. We identified some features typical of elite controllers, including high magnitude HIV-specific responses and beneficial HLA. In addition, we made the atypical finding of pre-infection HIV-specific immunity in one elite controller, that may have contributed to very early viral control. This report highlights the importance of studying HIV controllers in high incidence settings. The online version of this article (10.1186/s12879-018-2961-8) contains supplementary material, which is available to authorized users.
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来自精英控制器的CD4（+）T细胞中HIV-1逆转录的细胞内抑制剂。
影响因子：
30.3
作者：
Leng J;Ho HP;Buzon MJ;Pereyra F;Walker BD;Yu XG;Chang EJ;Lichterfeld M
通讯作者：
Lichterfeld M
影响因子：
3.7
作者：
Strain MC;Lada SM;Luong T;Rought SE;Gianella S;Terry VH;Spina CA;Woelk CH;Richman DD
通讯作者：
Richman DD
影响因子：
30.8
作者：
Martin, Maureen P.;Qi, Ying;Carrington, Mary
通讯作者：
Carrington, Mary
影响因子：
3.7
作者：
van Loggerenberg F;Mlisana K;Williamson C;Auld SC;Morris L;Gray CM;Abdool Karim Q;Grobler A;Barnabas N;Iriogbe I;Abdool Karim SS;CAPRISA 002 Acute Infection Study Team
通讯作者：
CAPRISA 002 Acute Infection Study Team
DOI：
10.1126/science.1193748
发表时间：
2010-09-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Abdool Karim Q;Abdool Karim SS;Frohlich JA;Grobler AC;Baxter C;Mansoor LE;Kharsany AB;Sibeko S;Mlisana KP;Omar Z;Gengiah TN;Maarschalk S;Arulappan N;Mlotshwa M;Morris L;Taylor D;CAPRISA 004 Trial Group
通讯作者：
CAPRISA 004 Trial Group