Dual role of α-defensin-1 in anti–HIV-1 innate immunity

We present a review and comparison of several recent differential equations models of treatment of HIV-1 infection. We seek to clarify the role of the natural anti-HIV immune response and determine its effect upon optimal treatment schemes. In this paper, we consider systems in which treatment is expressed as a forcing function, as well as those in which we determine optimal treatment via control theoretic techniques. The primary goal of this study is to compare treatment schemes for systems in which a natural nonconstant immune response of the patient is considered explicitly with those that consider implicitly a constant non-specific immune response. We find that when the natural immune response can be boosted sufficiently, drug levels may not need to be as high as previously supposed. This implies that a treatment scenario in which intervals of drug treatment are alternated with some form of immune-boosting therapy may be highly beneficial in terms of reducing toxicity to the patient. Additionally, in developing countries where HIV infection is widespread and sufficient funds are not available to supply rigourous drug regimens, the implications of these models are profound, as they suggest methods of treating HIV at a minimal cost.

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The role of the glycosyl moiety of myricetin derivatives in anti-HIV-1 activity in vitro

AIDS Research and Therapy ◽

10.1186/s12981-017-0183-6 ◽

2017 ◽

Vol 14 (1) ◽

Cited By ~ 16

Author(s):

Joseph T. Ortega ◽

Alirica I. Suárez ◽

Maria L. Serrano ◽

Jani Baptista ◽

Flor H. Pujol ◽

...

Keyword(s):

Anti Hiv ◽

Hiv 1

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Role of the M2 Subunit of Ribonucleotide Reductase in Regulation by Hydroxyurea of the Activity of the Anti-HIV-1 Agent 2′,3′-Dideoxyinosine

Biochemical Pharmacology ◽

10.1016/s0006-2952(98)00127-0 ◽

1998 ◽

Vol 56 (1) ◽

pp. 105-112 ◽

Cited By ~ 12

Author(s):

Wen-Yi Gao ◽

Bing-Sen Zhou ◽

David G Johns ◽

Hiroaki Mitsuya ◽

Yun Yen

Keyword(s):

Ribonucleotide Reductase ◽

Anti Hiv ◽

Hiv 1

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Role of MxB in Alpha Interferon-Mediated Inhibition of HIV-1 Infection

Journal of Virology ◽

10.1128/jvi.00422-18 ◽

2018 ◽

Vol 92 (17) ◽

Cited By ~ 10

Author(s):

Bin Xu ◽

Qinghua Pan ◽

Chen Liang

Keyword(s):

G Protein ◽

Transmembrane Protein ◽

Alpha Interferon ◽

Wild Type Virus ◽

Target Cells ◽

Type I ◽

Wide Range ◽

Anti Hiv ◽

Hiv 1

ABSTRACTType I interferon inhibits viruses through inducing the expression of antiviral proteins, including the myxovirus resistance (Mx) proteins. Compared to the human MxA protein, which inhibits a wide range of viruses, the MxB protein has been reported to specifically inhibit primate lentiviruses, including HIV-1, and herpesviruses. Further, the role of endogenous MxB in alpha interferon-mediated inhibition of HIV-1 infection was questioned by a recent study showing that MxB knockout did not increase the level of infection by HIV-1 which carried the G protein of vesicular stomatitis virus (VSV), allowing infection of CD4-negative HT1080 cells. In order to further examine the anti-HIV-1 activity of endogenous MxB, we have used CRISPR/Cas9 to deplete MxB in different cell lines and observed a substantial restoration of HIV-1 infection in the presence of alpha interferon treatment. However, this rescue effect of MxB knockout became much less pronounced when infection was performed with HIV-1 carrying the VSV G protein. Interestingly, a CRISPR/Cas9 knockout screen of alpha interferon-stimulated genes in U87-MG cells revealed that the genes for interferon-induced transmembrane protein 2 (IFITM2) and IFITM3 inhibited VSV G-pseudotyped HIV-1 much more strongly than the rest of the genes tested, including the gene for MxB. Therefore, our results demonstrate the importance of MxB in alpha interferon-mediated inhibition of HIV-1 infection, which, however, can be underestimated if infection is performed with VSV G protein-pseudotyped HIV-1, due to the high sensitivity of VSV G-mediated infection to inhibition by IFITM proteins.IMPORTANCEThe results of this study reconcile the controversial reports regarding the anti-HIV-1 function of alpha interferon-induced MxB protein. In addition to the different cell types that may have contributed to the different observations, our data also suggest that VSV G protein-pseudotyped HIV-1 is much less inhibited by alpha interferon-induced MxB than HIV-1 itself is. Our results clearly demonstrate an important contribution of MxB to alpha interferon-mediated inhibition of HIV-1 in CD4+T cells, which calls for using HIV-1 target cells and wild-type virus to test the relevance of the anti-HIV-1 activity of endogenous MxB and other restriction factors.

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Alpha Interferon Potently Enhances the Anti-Human Immunodeficiency Virus Type 1 Activity of APOBEC3G in Resting Primary CD4 T Cells

Journal of Virology ◽

10.1128/jvi.00206-06 ◽

2006 ◽

Vol 80 (15) ◽

pp. 7645-7657 ◽

Cited By ~ 107

Author(s):

Keyang Chen ◽

Jialing Huang ◽

Chune Zhang ◽

Sophia Huang ◽

Giuseppe Nunnari ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Innate Immunity ◽

T Cells ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cd4 T Cells ◽

Immunodeficiency Virus ◽

Anti Hiv ◽

Hiv 1

ABSTRACT The interferon (IFN) system, including various IFNs and IFN-inducible gene products, is well known for its potent innate immunity against wide-range viruses. Recently, a family of cytidine deaminases, functioning as another innate immunity against retroviral infection, has been identified. However, its regulation remains largely unknown. In this report, we demonstrate that through a regular IFN-α/β signal transduction pathway, IFN-α can significantly enhance the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) in human primary resting but not activated CD4 T cells and the amounts of APOBEC3G associated with a low molecular mass. Interestingly, short-time treatments of newly infected resting CD4 T cells with IFN-α will significantly inactivate human immunodeficiency virus type 1 (HIV-1) at its early stage. This inhibition can be counteracted by APOBEC3G-specific short interfering RNA, indicating that IFN-α-induced APOBEC3G plays a key role in mediating this anti-HIV-1 process. Our data suggest that APOBEC3G is also a member of the IFN system, at least in resting CD4 T cells. Given that the IFN-α/APOBEC3G pathway has potent anti-HIV-1 capability in resting CD4 T cells, augmentation of this innate immunity barrier could prevent residual HIV-1 replication in its native reservoir in the post-highly active antiretroviral therapy era.

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