HCMV modulation of cellular PI3K/AKT/mTOR signaling: New opportunities for therapeutic intervention?
HCMV modulation of cellular PI3K/AKT/mTOR signaling: New opportunities for therapeutic intervention?
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DOI：
10.1016/j.antiviral.2019.01.009
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发表时间：
2019-03-01
影响因子：
7.6
通讯作者：
Chan, Gary
中科院分区：
文献类型：
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作者：
Altman, Aaron M.;Mahmud, Jamil;Chan, Gary
人巨细胞病毒（HCMV）仍然是国内外主要的公共卫生负担。目前批准的治疗方法，包括更昔洛韦，只有适度的有效性，许多移植患者患有各种副作用。目前抗HCMV药物功效的主要障碍是其抗病毒作用仅限于病毒复制的裂解阶段。因此，病毒生命周期的非裂解阶段仍然是与移植受体相关的HCMV感染的主要来源，并最终成为发病和死亡的原因。虽然阻断裂解性复制的新抗病毒药物的研究仍在继续，但HCMV独特生命周期的休眠阶段需要同时评估新的治疗干预措施。在这篇综述中，我们将研究PI 3 K/Akt/mTOR信号轴在HCMV生命周期的不同阶段所起的作用，并描述靶向这一细胞通路作为抗病毒策略的优势。特别是，我们专注于利用独特的修改HCMV赋予的PI 3 K/Akt/mTOR通路在单核细胞的静止感染，这在病毒的传播策略中起着至关重要的作用的潜力。
Human cytomegalovirus (HCMV) remains a major public health burden domestically and abroad. Current approved therapies, including ganciclovir, are only moderately efficacious, with many transplant patients suffering from a variety of side effects. A major impediment to the efficacy of current anti-HCMV drugs is their antiviral effects are restricted to the lytic stage of viral replication. Consequently, the non-lytic stages of the viral lifecycle remain major sources of HCMV infection associated with transplant recipients and ultimately the cause of morbidity and mortality. While work continues on new antivirals that block lytic replication, the dormant stages of HCMV's unique lifecycle need to be concurrently assessed for new therapeutic interventions. In this review, we will examine the role that the PI3K/Akt/mTOR signaling axis plays during the different stages of HCMV's lifecycle, and describe the advantages of targeting this cellular pathway as an antiviral strategy. In particular, we focus on the potential of exploiting the unique modifications HCMV imparts on the PI3K/Akt/mTOR pathway during quiescent infection of monocytes, which serve an essential role in the dissemination strategy of the virus.