Viral reservoirs of HIV-1 are a major obstacle for curing AIDS. The novel animal models that can be directly infected with HIV-I will contribute to develop effective strategies for eradicating infections. Here, we ino...Viral reservoirs of HIV-1 are a major obstacle for curing AIDS. The novel animal models that can be directly infected with HIV-I will contribute to develop effective strategies for eradicating infections. Here, we inoculated 4 northern pig-tailed macaques （NPM） with the HIV-1 strain HIV-1NL4.3 and moni- tored the infection for approximately 3 years （150 weeks）. The HIV-l-infected NPMs showed transient viremia for about 10 weeks after infection. However, cell-associated proviral DNA and viral RNA persisted in the peripheral blood and lymphoid organs for about 3 years. Moreover, replication-competent HIV-1 could be successfully recovered from peripheral blood mononuclear cells （PBMCs） during long-term infection. The numbers of resting CD4~ T cells in HIV-1 infected NPMs harboring proviruses fell within a range of 2- to 3-1oglo per million cells, and these proviruses could be reactivated both ex vivo and in vivo in response to co-stimulation with the latency-reversing agents JQ1 and prostratin. Our results suggested that NPMs can be infected with HIV-1 and a long-term viral reservoir was formed in NPMs, which might serve as a potential model for HIV-1 reservoir research.展开更多
Nipah Virus (NiV), a member of the Paramyxoviridae family, is one of the most infectious zoonotic viruses in Southeast Asia. First recorded in Malaysia in 1998, the NiV outbreak infected hundreds of people, with an al...Nipah Virus (NiV), a member of the Paramyxoviridae family, is one of the most infectious zoonotic viruses in Southeast Asia. First recorded in Malaysia in 1998, the NiV outbreak infected hundreds of people, with an almost 50% death rate. The virus is transmitted through direct contact with contaminated subjects and infecting the human respiratory system. Ephrin B2 and B3, the surface glycoproteins on the host cell, have been the primary and the most effective route for viral entrance. Binding with viral surface G protein, the F protein triggers, enabling viral-host fusion. Until now, NiV vaccines are not yet available in the public market, however, preventions such as avoiding direct contact and masking are advised.展开更多
Host immune surveillance can achieve powerful clearance of infectious pathogens.Acute human immunodeficiency virus type I(HIV-1)infection can establish viral reservoirs in humans,and persistent chronic activation by t...Host immune surveillance can achieve powerful clearance of infectious pathogens.Acute human immunodeficiency virus type I(HIV-1)infection can establish viral reservoirs in humans,and persistent chronic activation by the virus exhausts the immune system and ultimately causes acquired immunodeficiency syndrome.Although antiretroviral therapy(ART)can reduce the viral load and viremia in patients,latent HIV-1 reservoirs are still the biggest challenge that needs to be overcome to eradicate the virus.However,the low or absent viral antigen expression and epitope mutation caused during durable ART result in host immune escape and reservoir cell inaccessibility.In addition,durable ART accompanied by inflammation and persistent activation of immune cells,especially dysfunction and/or exhaustion of T cells.With the development of immunology,genetics,and genetic engineering technology,researchers can construct chimeric antigen receptors(CARs)to modify immune cells to enhance HIV clearance.The important research goals of creating CARs tomodify natural killer(NK)and T cells are an attempt to enhance the functional effects of immune cells and restore the function of the immune system.This article reviews the latent characteristics of HIV,the development of CARmolecules,and the strategies for reprogramming T cells and NK cells with CARs,and aims to clear the HIV reservoirs and related potential problems.展开更多
基金supported by the National Basic Research Program of China (2012CBA01305)the National Natural Science Foundation of China (81172876+11 种基金 81571606 81471620 U0832601 30671960)the 13th Five-Year Key Scientific and Technological Program of China (2017ZX10304402002-004 2017ZX10202102-001-005)the Knowledge Innovation Program of the Chinese Academy of Sciences (KSCX2-EW-R-13 KJZD-EW-L10-02 CASIMM0320163020)the National Key Research & Development Plan (2016YFC1201000)Yunnan Applicative and Basic Research Program (2014FB181 201501PH00015)
文摘Viral reservoirs of HIV-1 are a major obstacle for curing AIDS. The novel animal models that can be directly infected with HIV-I will contribute to develop effective strategies for eradicating infections. Here, we inoculated 4 northern pig-tailed macaques （NPM） with the HIV-1 strain HIV-1NL4.3 and moni- tored the infection for approximately 3 years （150 weeks）. The HIV-l-infected NPMs showed transient viremia for about 10 weeks after infection. However, cell-associated proviral DNA and viral RNA persisted in the peripheral blood and lymphoid organs for about 3 years. Moreover, replication-competent HIV-1 could be successfully recovered from peripheral blood mononuclear cells （PBMCs） during long-term infection. The numbers of resting CD4~ T cells in HIV-1 infected NPMs harboring proviruses fell within a range of 2- to 3-1oglo per million cells, and these proviruses could be reactivated both ex vivo and in vivo in response to co-stimulation with the latency-reversing agents JQ1 and prostratin. Our results suggested that NPMs can be infected with HIV-1 and a long-term viral reservoir was formed in NPMs, which might serve as a potential model for HIV-1 reservoir research.
文摘Nipah Virus (NiV), a member of the Paramyxoviridae family, is one of the most infectious zoonotic viruses in Southeast Asia. First recorded in Malaysia in 1998, the NiV outbreak infected hundreds of people, with an almost 50% death rate. The virus is transmitted through direct contact with contaminated subjects and infecting the human respiratory system. Ephrin B2 and B3, the surface glycoproteins on the host cell, have been the primary and the most effective route for viral entrance. Binding with viral surface G protein, the F protein triggers, enabling viral-host fusion. Until now, NiV vaccines are not yet available in the public market, however, preventions such as avoiding direct contact and masking are advised.
基金supported by the National Science and Technology Major Project of China(2018ZX10301-101)the National Natural Science Foundation of China(32060177).
文摘Host immune surveillance can achieve powerful clearance of infectious pathogens.Acute human immunodeficiency virus type I(HIV-1)infection can establish viral reservoirs in humans,and persistent chronic activation by the virus exhausts the immune system and ultimately causes acquired immunodeficiency syndrome.Although antiretroviral therapy(ART)can reduce the viral load and viremia in patients,latent HIV-1 reservoirs are still the biggest challenge that needs to be overcome to eradicate the virus.However,the low or absent viral antigen expression and epitope mutation caused during durable ART result in host immune escape and reservoir cell inaccessibility.In addition,durable ART accompanied by inflammation and persistent activation of immune cells,especially dysfunction and/or exhaustion of T cells.With the development of immunology,genetics,and genetic engineering technology,researchers can construct chimeric antigen receptors(CARs)to modify immune cells to enhance HIV clearance.The important research goals of creating CARs tomodify natural killer(NK)and T cells are an attempt to enhance the functional effects of immune cells and restore the function of the immune system.This article reviews the latent characteristics of HIV,the development of CARmolecules,and the strategies for reprogramming T cells and NK cells with CARs,and aims to clear the HIV reservoirs and related potential problems.
