Origin of rebound virus in chronically SIV-infected Rhesus monkeys following treatment discontinuation.
Origin of rebound virus in chronically SIV-infected Rhesus monkeys following treatment discontinuation.
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DOI：
10.1038/s41467-020-19254-2
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发表时间：
2020-10-27
影响因子：
16.6
通讯作者：
Barouch DH
中科院分区：
文献类型：
--
作者：
Liu PT;Keele BF;Abbink P;Mercado NB;Liu J;Bondzie EA;Chandrashekar A;Borducchi EN;Hesselgesser J;Mish M;Chin G;Bekerman E;Geleziunas R;Barouch DH
HIV-1感染者停止抗逆转录病毒治疗(ART)后的病毒反弹被认为源于一小部分携带有复制能力的前病毒的CD4+T细胞。然而，反弹病毒的来源和性质仍不清楚。最近的研究表明，反弹病毒并不直接起源于单个潜伏的前病毒，而是涉及多个前病毒的重组事件。在这里，我们评估了16只ART抑制的、慢性SIV感染的恒河猴在ART停用后反弹病毒的来源。我们在ART启动前、ART抑制期间和病毒反弹之后对这些动物中的病毒RNA和病毒DNA进行了测序，并将ART停用后反弹的病毒RNA与ART抑制期间外周血和淋巴结单个核细胞(PBMC和LNMC)中的近全长病毒DNA进行了比较。在ART抑制过程中，初始反弹病毒的序列与PBMC和LNMC中的病毒DNA序列非常匹配。重组病毒在最初的反弹病毒群体中很少见，但在病毒反弹后2-4周内迅速出现。这些数据表明，ART抑制期间PBMC和LNMC中完整的前病毒DNA可能是ART停用后慢性SIV感染猕猴病毒反弹的直接来源。停用抗逆转录病毒疗法(ART)后反弹的HIV-1病毒的来源和性质仍不清楚。在这里，刘等人。提示ART抑制过程中外周血和淋巴结单个核细胞中完整的前病毒DNA可能是ART停药后病毒反弹的来源。
Viral rebound following antiretroviral therapy (ART) discontinuation in HIV-1-infected individuals is believed to originate from a small pool of CD4+ T cells harboring replication-competent provirus. However, the origin and nature of the rebound virus has remained unclear. Recent studies have suggested that rebound virus does not originate directly from individual latent proviruses but rather from recombination events involving multiple proviruses. Here we evaluate the origin of rebound virus in 16 ART-suppressed, chronically SIV-infected rhesus monkeys following ART discontinuation. We sequence viral RNA and viral DNA in these animals prior to ART initiation, during ART suppression, and following viral rebound, and we compare rebound viral RNA after ART discontinuation with near full-length viral DNA from peripheral blood and lymph node mononuclear cells (PBMC and LNMC) during ART suppression. Sequences of initial rebound viruses closely match viral DNA sequences in PBMC and LNMC during ART suppression. Recombinant viruses are rare in the initial rebound virus populations but arise quickly within 2–4 weeks after viral rebound. These data suggest that intact proviral DNA in PBMC and LNMC during ART suppression is likely the direct origin of viral rebound in chronically SIV-infected rhesus monkeys following ART discontinuation. The origin and nature of rebound HIV-1 virus following antiretroviral therapy (ART) discontinuation still remains unclear. Here, Liu et al. suggest that intact proviral DNA in peripheral blood and lymph node mononuclear cells during ART suppression likely is the source of viral rebound following ART discontinuation.
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影响因子：
64.8
作者：
Borducchi, Erica N.;Cabral, Crystal;Stephenson, Kathryn E.;Liu, Jinyan;Abbink, Peter;Ng'ang'a, David;Nkolola, Joseph P.;Brinkman, Amanda L.;Peter, Lauren;Lee, Benjamin C.;Jimenez, Jessica;Jetton, David;Mondesir, Jade;Mojta, Shanell;Chandrashekar, Abishek;Molloy, Katherine;Alter, Galit;Gerold, Jeffrey M.;Hill, Alison L.;Lewis, Mark G.;Pau, Maria G.;Schuitemaker, Hanneke;Hesselgesser, Joseph;Geleziunas, Romas;Kim, Jerome H.;Robb, Merlin L.;Michael, Nelson L.;Barouch, Dan H.
通讯作者：
Barouch, Dan H.
DOI：
10.1073/pnas.1308313110
发表时间：
2013-12-17
影响因子：
11.1
作者：
Josefsson, Lina;von Stockenstrom, Susanne;Palmer, Sarah
通讯作者：
Palmer, Sarah
影响因子：
15.9
作者：
Lee, Guinevere Q.;Orlova-Fink, Nina;Lichterfeld, Mathias
通讯作者：
Lichterfeld, Mathias
DOI：
10.1073/pnas.0736332100
发表时间：
2003-04-15
影响因子：
11.1
作者：
Strain, MC;G端nthard, HF;Wong, JK
通讯作者：
Wong, JK
影响因子：
64.5
作者：
Ho YC;Shan L;Hosmane NN;Wang J;Laskey SB;Rosenbloom DI;Lai J;Blankson JN;Siliciano JD;Siliciano RF
通讯作者：
Siliciano RF