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胸腺/肝脏联合重症联合免疫缺陷-人源化小鼠:一种用于研究多药疗法对血浆病毒血症及淋巴组织中人类免疫缺陷病毒复制的体内效应的系统。

thy/liv-SCID-hu mice: a system for investigating the in vivo effects of multidrug therapy on plasma viremia and human immunodeficiency virus replication in lymphoid tissues.

作者信息

Pettoello-Mantovani M, Kollmann T R, Katopodis N F, Raker C, Kim A, Yurasov S, Wiltshire H, Goldstein H

机构信息

Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

出版信息

J Infect Dis. 1998 Feb;177(2):337-46. doi: 10.1086/514214.

DOI:10.1086/514214
PMID:9466519
Abstract

Modified, human immunodeficiency virus (HIV)-inoculated thy/liv-SCID-hu mice were used to evaluate the in vivo efficacy of antiretroviral drugs. Ritonavir treatment alone initially suppressed plasma viremia, but the viremia recurred with the appearance of ritonavir-resistant HIV isolates. Multidrug therapy suppressed plasma HIV RNA to undetectable levels; however, plasma viremia returned after therapy was stopped, showing that the therapy did not completely suppress HIV infection in the thymic implant. When thy/liv-SCID-hu mice were treated with a combination of zidovudine, lamivudine, and ritonavir immediately after inoculation with HIV, cocultures of the thymic implants remained negative for HIV even 1 month after therapy was discontinued, suggesting that acute treatment can prevent the establishment of HIV infection. Thus, these modified thy/liv-SCID-hu mice should prove to be a useful system for evaluating the effectiveness of different antiretroviral therapies on acute and chronic HIV infection.

摘要

使用经修饰的接种了人类免疫缺陷病毒(HIV)的thy/liv-SCID-hu小鼠来评估抗逆转录病毒药物的体内疗效。单独使用利托那韦治疗最初可抑制血浆病毒血症,但随着利托那韦耐药HIV毒株的出现,病毒血症复发。联合药物治疗可将血浆HIV RNA抑制到检测不到的水平;然而,治疗停止后血浆病毒血症又复发,表明该治疗并未完全抑制胸腺植入物中的HIV感染。当thy/liv-SCID-hu小鼠在接种HIV后立即用齐多夫定、拉米夫定和利托那韦联合治疗时,即使在治疗停止1个月后,胸腺植入物的共培养物对HIV仍呈阴性,这表明急性治疗可预防HIV感染的建立。因此,这些经修饰的thy/liv-SCID-hu小鼠应被证明是评估不同抗逆转录病毒疗法对急性和慢性HIV感染有效性的有用系统。

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