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Basic Characteristics of Mutations
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Mutation Site
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L74V |
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Mutation Site Sentence
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The most frequent mutation of resistance to NRTI worldwide is M184V/I, followed by K65R/N, L74V/I, Y115F, and Q151M, and the most prevalent for FSU_A is M184V, followed by K65R/N. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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gag-pol:155348
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Genotype/Subtype
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HIV-1 A |
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Viral Reference
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HXB2
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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NRTIs |
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Location
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former Soviet Union |
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Literature Information
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PMID
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31885806
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Title
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HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist
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Author
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Bayurova E,Jansons J,Skrastina D,Smirnova O,Mezale D,Kostyusheva A,Kostyushev D,Petkov S,Podschwadt P,Valuev-Elliston V,Sasinovich S,Korolev S,Warholm P,Latanova A,Starodubova E,Tukhvatulin A,Latyshev O,Selimov R,Metalnikov P,Komarov A,Ivanova O,Gorodnicheva T,Kochetkov S,Gottikh M,Strumfa I,Ivanov A,Gordeychuk I,Isaguliants M
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Journal
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Oxidative medicine and cellular longevity
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Journal Info
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2019 Dec 2;2019:6016278
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Abstract
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HIV-induced immune suppression results in the high prevalence of HIV/AIDS-associated malignancies including Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer. HIV-infected people are also at an increased risk of ""non-AIDS-defining"" malignancies not directly linked to immune suppression but associated with viral infections. Their incidence is increasing despite successful antiretroviral therapy. The mechanism behind this phenomenon remains unclear. Here, we obtained daughter clones of murine mammary gland adenocarcinoma 4T1luc2 cells expressing consensus reverse transcriptase of HIV-1 subtype A FSU_A strain (RT_A) with and without primary mutations of drug resistance. In in vitro tests, mutations of resistance to nucleoside inhibitors K65R/M184V reduced the polymerase, and to nonnucleoside inhibitors K103N/G190S, the RNase H activities of RT_A. Expression of these RT_A variants in 4T1luc2 cells led to increased production of the reactive oxygen species (ROS), lipid peroxidation, enhanced cell motility in the wound healing assay, and upregulation of expression of Vimentin and Twist. These properties, particularly, the expression of Twist, correlated with the levels of expression RT_A and/or the production of ROS. When implanted into syngeneic BALB/C mice, 4T1luc2 cells expressing nonmutated RT_A demonstrated enhanced rate of tumor growth and increased metastatic activity, dependent on the level of expression of RT_A and Twist. No enhancement was observed for the clones expressing mutated RT_A variants. Plausible mechanisms are discussed involving differential interactions of mutated and nonmutated RTs with its cellular partners involved in the regulation of ROS. This study establishes links between the expression of HIV-1 RT, production of ROS, induction of EMT, and enhanced propagation of RT-expressing tumor cells. Such scenario can be proposed as one of the mechanisms of HIV-induced/enhanced carcinogenesis not associated with immune suppression.
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Sequence Data
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DQ207944;EF589042;EF589043;EF589039;EF589044;EF589040;EF589041;EF545108;JQ292892;AY500393;JQ292895;JQ292896;JQ292897;JQ292898;JQ292899;JQ292900;JQ292891;KF716491;KF716492;FJ864679;JQ292893;JQ292894;JX500696;JX500695;JX500694;AF413987;DQ823358;DQ823357;DQ823361;DQ823365;DQ823366;DQ823367;DQ823359;DQ823356;DQ823360;AY829209;AY829210;AY829211;AY829212;AY829203;AY829205;AY829206;AY829208;KT983615
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