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Kinases: Understanding Their Role in HIV Infection.

ABSTRACT: Antiviral drugs currently on the market primarily target proteins encoded by specific viruses. The drawback of these drugs is that they lack antiviral mechanisms that account for resistance or viral mutation. Thus, there is a pressing need for researchers to explore and investigate new therapeutic agents with other antiviral strategies. Viruses such as the human immunodeficiency virus (HIV) alter canonical signaling pathways to create a favorable biochemical environment for infectivity. We used Qiagen Ingenuity Pathway Analysis (IPA) software to review the function of several cellular kinases and the resulting perturbed signaling pathways during HIV infection such as NF-?B signaling. These host cellular kinases such as ADK, PKR, MAP3K11 are involved during HIV infection at various stages of the life cycle. Additionally IPA analysis indicated that these modified host cellular kinases are known to have interactions with each other especially AKT1, a serine/threonine kinase involved in multiple pathways. We present a list of cellular host kinases and other proteins that interact with these kinases. This approach to understanding the relationship between HIV infection and kinase activity may introduce new drug targets to arrest HIV infectivity.

SUBMITTER: De Martini W

PROVIDER: S-EPMC7118713 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Kinases: Understanding Their Role in HIV Infection.

De Martini William W Rahman Roksana R Ojegba Eduvie E Jungwirth Emily E Macias Jasmine J Ackerly Frederick F Fowler Mia M Cottrell Jessica J Chu Tinchun T Chang Sulie L SL

World journal of AIDS 20190909 3

Antiviral drugs currently on the market primarily target proteins encoded by specific viruses. The drawback of these drugs is that they lack antiviral mechanisms that account for resistance or viral mutation. Thus, there is a pressing need for researchers to explore and investigate new therapeutic agents with other antiviral strategies. Viruses such as the human immunodeficiency virus (HIV) alter canonical signaling pathways to create a favorable biochemical environment for infectivity. We used ...[more]

PMID: 32257606

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Project description:Despite an augmented research effort and scale-up of highly active antiretroviral therapy, a high prevalence of HIV-1-associated neurocognitive disorders (HAND) persists in the HIV-infected population. Nearly 50 % of all HIV-1-infected individuals suffer from a neurocognitive disorder due to neural and synaptodendritic damage. Challenges in HAND research, including limited availability of brain tissue from HIV patients, variation in HAND study protocols, and virus genotyping inconsistency and errors, however, have resulted in studies with insufficient power to delineate molecular mechanisms underlying HAND pathogenesis. There exists, therefore, a great need for a reliable and centralized resource specific to HAND research, particularly for epidemiological study and surveillance in resource-limited countries where severe forms of HAND persist.To address the aforementioned imperative need, here we present the HAND Database, a resource containing well-curated and up-to-date HAND virus information and associated clinical and epidemiological data. This database provides information on 5,783 non-redundant HIV-1 sequences from global HAND research published to date, representing a total of 163 unique individuals that have been assessed for HAND. A user-friendly interface allows for flexible searching, filtering, browsing, and downloading of data. The most comprehensive database of its kind, the HAND Database not only bolsters current HAND research by increasing sampling power and reducing study biases caused by protocol variation and genotyping inconsistency, it allows for comparison between HAND studies across different dimensions. Development of the HAND Database has also revealed significant knowledge gaps in HIV-driven neuropathology. These gaps include inadequate sequencing of viral genes beyond env, lack of HAND viral data from HIV epidemiologically important regions including Asian and Sub-Saharan African countries, and biased sampling toward the male gender, all factors that impede efforts toward providing an improved quality of life to HIV-infected individuals, and toward elimination of viruses in the brain.Our aim with the HAND database is to provide researchers in both the HIV and neuroscience fields a comprehensive and rigorous data source toward better understanding virus compartmentalization and to help in design of improved strategies against HAND viruses. We also expect this resource, which will be updated on a regular basis, to be useful as a reliable reference for further HAND epidemiology studies. The HAND Database is freely available and accessible online at http://www.handdatabase.org .

Project description:PURPOSE OF REVIEW:This article explores new data from recent studies addressing the role of coinfections in immune activation in HIV-1-infected patients, with a focus on immune reconstitution inflammatory syndrome (IRIS), an aberrant inflammatory response occurring shortly after antiretroviral therapy (ART) initiation. RECENT FINDINGS:Chronic HIV infection is associated with several coinfections that contribute to immune activation in various settings including early after ART initiation in the most noticeable form of IRIS and also in chronic-treated infection, with chronic viral infections like cytomegalovirus and hepatitis C or hepatitis B virus contributing to immune activation and also morbidity and mortality. Expanding on older studies, the role of T cells in IRIS has been further elucidated with evidence of more pronounced effector activity in patients with IRIS that may be leading to excessive tissue disorder. Newer studies are also continuing to shed light on the role of myeloid cells as well as the contribution of antigen load in IRIS. In addition, preliminary data are beginning to suggest a possible role of inflammasome formation in IRIS. In cryptococcal IRIS, the role of activated immune cells (T cell and myeloid) and biomarkers were evaluated in more detail at the site of infection (cerebrospinal fluid). Finally, important differences of patients developing IRIS versus those who die from tuberculosis despite ART initiation were reported, a distinction that may have important implications for participant selection in studies aiming to prevent IRIS with immunosuppressive agents. SUMMARY:Better understanding of the role of opportunistic infections at ART initiation and IRIS pathogenesis will assist in improved strategies for prevention and treatment. The long-term consequences of IRIS remain unclear. Chronic viral coinfections with herpesviruses and hepatitis C virus are important factors in persistent immune activation in chronic-treated HIV.

Dataset Information

Kinases: Understanding Their Role in HIV Infection.

Publications

Kinases: Understanding Their Role in HIV Infection.

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