Ⅰ型干扰素在HIV-1感染中的作用具有两面性
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摘要
Ⅰ型干扰素(以下简称为干扰素)是重要的抗病毒因子,也是临床上治疗病毒感染性疾病的药物.然而,干扰素在HIV感染中的作用一直存在争议.最近在HIV感染的人源化小鼠模型中发现,干扰素具有抑制HIV复制和破坏抗病毒免疫的双重作用.在抗病毒药物治疗的同时,注射干扰素受体的阻断抗体显著提高抗HIV特异性免疫反应,延缓停药后病毒反弹.这些研究结果提示,干扰素有望成为研发治疗艾滋病新型药物的靶点.
Type Ⅰ interferons(IFN-Ⅰs) are essential for antiviral immune responses and have been developed for the treatment of various viral infections. However, the roles of IFN-Ⅰs in HIV infection remain elusive.Recent data from HIV-infected humanized mice show that IFN-Ⅰs play both protective role by suppressing HIV replication and detrimental role by inhibiting anti-HIV immune responses. Administration of IFN-Ⅰ receptor(IFNAR)blocking antibody in the presence of antiretroviral therapy(ART) rescues anti-HIV immune responses and delays HIV rebound upon the cessation of antiviral drugs. Thus, IFN-Ⅰs provide a potential target for the development of novo drugs treating HIV infection.
Type Ⅰ interferons(IFN-Ⅰs) are essential for antiviral immune responses and have been developed for the treatment of various viral infections. However, the roles of IFN-Ⅰs in HIV infection remain elusive.Recent data from HIV-infected humanized mice show that IFN-Ⅰs play both protective role by suppressing HIV replication and detrimental role by inhibiting anti-HIV immune responses. Administration of IFN-Ⅰ receptor(IFNAR)blocking antibody in the presence of antiretroviral therapy(ART) rescues anti-HIV immune responses and delays HIV rebound upon the cessation of antiviral drugs. Thus, IFN-Ⅰs provide a potential target for the development of novo drugs treating HIV infection.
引文
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[3]Embretson J,Zupancic M,Ribas J L,et al.Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS.Nature,1993,362(6418):359-362
[4]Pantaleo G,Graziosi C,Demarest J F,et al.HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease.Nature,1993,362(6418):355-358
[5]Mccune J M.The dynamics of CD4+T-cell depletion in HIV disease.Nature,2001,410(6831):974-979
[6]Silvestri G.AIDS pathogenesis:a tale of two monkeys.Journal of Medical Primatology,2008,37(Suppl 2):6-12
[7]Pestka S.Purification and cloning of interferon alpha.Current Topics in Microbiology and Immunology,2007,316(1):23-37
[8]Schneider W M,Chevillotte M D,Rice C M.Interferon-stimulated genes:a complex web of host defenses.Annu Rev Immunol,2014,32(1):513-545
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[11]Carlson R J,Doucette J R,Knox K,et al.Pharmacogenomics of interferon-beta in multiple sclerosis:what has been accomplished and how can we ensure future progress?Cytokine&Growth Factor Reviews,2015,26(2):249-261
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[14]Stacey A R,Norris P J,Qin L,et al.Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection,in contrast to more modest and delayed responses in acute hepatitis B and C virus infections.Journal of Virology,2009,83(8):3719-3733
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