Recent advances targeting innate immunity‐mediated therapies against HIV‐1 infection

Shankar, Esaki Muthu; Velu, Vijayakumar; Vignesh, Ramachandran; Vijayaraghavalu, Sivakumar; Rukumani, Devi V.; Sabet, Negar Shafiei

doi:10.1111/j.1348-0421.2012.00485.x

Cited by 11 publications

(7 citation statements)

References 108 publications

(137 reference statements)

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“…A highly complex network of positive and negative signals from the co-stimulatory and co-inhibitory receptors regulates the outcome of virus-specific T-cell responses during acute and chronic viral infections [ 47 , 129 , 130 ]. Multiple inhibitory receptors are expressed in various levels on virus-specific CD8 + T cells (Figure 1 ) and play a major role in impairment of T-cell functionality during chronic viral infection [ 131 ].…”

Section: Reviewmentioning

confidence: 99%

“…However, only a few studies have demonstrated the simultaneous expression of several inhibitory receptors on HIV-specific CD8 + T cells. During chronic HIV infection, HIV-specific CD8 + T cells has been shown to express multiple inhibitory receptors such as PD-1, CD160, 2B4, TIM-3 and the expression of multiple inhibitory receptors correlates strongly with both HIV viral loads as well as with impaired cytokine production [ 29 , 130 , 135 - 137 ] (Figure 1 ). The increase and simultaneous expression of several co-inhibitory receptors on HIV-specific CD8 + T cells and the expression pattern of inhibitory receptors correlated positively with the degree of HIV-specific CD8 + T-cell exhaustion [ 29 ].…”

Section: Reviewmentioning

confidence: 99%

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Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options

et al. 2015

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Virus-specific CD8+ T cells play an important role in controlling viral infections including human immunodeficiency virus (HIV) infection. However, during chronic HIV infection, virus-specific CD8+ T cells undergo functional exhaustion, lose effector functions and fail to control viral infection. HIV-specific CD8 T cells expressing high levels of co-inhibitory molecule programmed death-1 (PD-1) during the chronic infection and are characterized by lower proliferation, cytokine production, and cytotoxic abilities. Although, antiretroviral therapy has resulted in dramatic decline in HIV replication, there is no effective treatment currently available to eradicate viral reservoirs or restore virus-specific T or B-cell functions that may complement ART in order to eliminate the virus. In recent years, studies in mice and non-human primate models of HIV infection demonstrated the functional exhaustion of virus-specific T and B cells could be reversed by blockade of interaction between PD-1 and its cognate ligands (PD-L1 and PD-L2). In this review, we discuss recent advances in our understanding of PD-1 pathway in HIV/SIV infection and discuss the beneficial effects of PD-1 blockade during chronic HIV/SIV infection and its potential role as immunotherapy for HIV/AIDS.

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Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options

et al. 2015

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“…Attempted strategies to target CD4 binding comprise soluble forms of CD4 (sCD4), CD4 mimetics, small molecular drugs against CD4 or the CD4bs on gp120, specific antibodies against CD4 or the CD4bs and CD4 downmodulators (for review see [46]). Interestingly, some mediators of innate immunity like defensins, small cationic peptides secreted from epithelial cells and neutrophils, also operate by interfering mainly with the gp120-CD4 interaction [47][48][49].…”

Section: The Primary Hiv Receptor Cd4 and Cd4-gp120 Inhibitorsmentioning

confidence: 99%

Targeting Cellular Cofactors in HIV Therapy

Dürr

Keppler

Christ

et al. 2014

Topics in Medicinal Chemistry

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Besides viral proteins cellular factors play a key role in the replication of the human immunodeficiency virus HIV-1. The outcome of virus replication is determined by the balance between the activity of a number of cellular dependency factors and restriction factors. Whereas the first are essential cofactors for diverse steps in the viral replication cycle, the latter counteract virus replication by sensing particular viral components as non-self, often as mediators of the innate immune system. Cellular cofactors include receptors for HIV-1 entry, LEDGF as cofactor for the viral integrase, the RNA helicase DDX3 involved in the nuclear export of unspliced viral RNAs, and diverse cellular kinases that promote viral replication. Cellular restriction factors are often antagonized by HIV-1 accessory proteins in order to counteract their restrictive function on viral replication. Although cellular cofactors in the HIV field are understood as factors promoting viral replication, we add a subchapter on the most important restriction factors (Trim5α, APOBEC3G, SAMHD1, and tetherin/BST-2). Today highly active antiretroviral therapy (HAART) mostly targets HIV proteins like reverse transcriptase, protease, or integrase to specifically interfere with virus replication. However, the identification of cellular cofactors and the increasing knowledge on their mode of action at R. Dürr and U. Dietrich (*) Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Paul-Ehrlich-Str. 42-44, 60596 Frankfurt, Germany e-mail: duerr@gsh.uni-frankfurt.de; ursula.dietrich@gsh.uni-frankfurt.de O. Keppler Institute of Medical Virology, Goethe University, Frankfurt, Germany e-mail: oliver.keppler@kgu.de F. Christ Laboratory for Molecular Virology and Gene Therapy, K.U. Leuven, Leuven, Belgium e-mail: frauke.christ@med.kuleuven.be E. Crespan, A. Garbelli, and G. Maga Institute of Molecular Genetics, IGM-CNR, Pavia, Italy e-mail: emmanuelecrespan@gmail.com; agarbelli@gmail.com; maga@igm.cnr.it defined steps in the HIV-1 replication cycle have opened new avenues towards the development of HIV-1 inhibitors. Here we summarize the most important cellular factors involved in HIV-1 replication along with therapeutic approaches developed to target them, preferentially without harming their normal cellular function.

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“…Some of the targets include ‘APOBEC 3G' that interferes with viral DNA synthesis, ‘Tetherin' that blocks viral release and TRIMα that destabilizes the HIV capsid and interferes with reverse transcription. 93,94,95,96,97 Another candidate target is ‘LEDGF/p75', an integrase enzyme cofactor, whose antagonists are being studied for their ability to suppress HIV replication. 98 Other possible ARV mechanisms involve the endogenously secreted antimicrobial peptides such as defensins, lactoferrins, secretory leukocyte protease inhibitor and Trappin-2/Elafin that all have shown to possess strong anti-HIV properties.…”

Section: New Intervention Strategiesmentioning

confidence: 99%

“…98 Other possible ARV mechanisms involve the endogenously secreted antimicrobial peptides such as defensins, lactoferrins, secretory leukocyte protease inhibitor and Trappin-2/Elafin that all have shown to possess strong anti-HIV properties. 95,96 …”

Section: New Intervention Strategiesmentioning

confidence: 99%

Thirty years of the human immunodeficiency virus epidemic and beyond

Younai

2013

Int J Oral Sci

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After more than 30 years of battling a global epidemic, the prospect of eliminating human immunodeficiency virus (HIV) as the most challenging infectious disease of the modern era is within our reach. Major scientific discoveries about the virus responsible for this immunodeficiency disease state, including its pathogenesis, transmission patterns and clinical course, have led to the development of potent antiretroviral drugs that offer great hopes in HIV treatment and prevention. Although these agents and many others still in development and testing are capable of effectively suppressing viral replication and survival, the medical management of HIV infection at the individual and the population levels remains challenging. Timely initiation of antiretroviral drugs, adherence to the appropriate therapeutic regimens, effective use of these agents in the pre and post-exposure prophylaxis contexts, treatment of comorbid conditions and addressing social and psychological factors involved in the care of individuals continue to be important considerations.

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Recent advances targeting innate immunity‐mediated therapies against HIV‐1 infection

Cited by 11 publications

References 108 publications

Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options

Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options

Targeting Cellular Cofactors in HIV Therapy

Thirty years of the human immunodeficiency virus epidemic and beyond

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