Influence of L-lysine amino acid on the HIV-1 RNA replication in vitro

Background Virus replication strongly depends on host metabolic machinery and essential cellular factors, in particular, on amino acid profiles. Amino acids play an important role in the pathogenesis of all virus-related infections both as basic substrates for protein synthesis and as regulators in...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Antiviral chemistry & chemotherapy 2015-02, Vol.24 (1), p.39-46
1. Verfasser: Butorov, Evgeny Vlad
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 46
container_issue 1
container_start_page 39
container_title Antiviral chemistry & chemotherapy
container_volume 24
creator Butorov, Evgeny Vlad
description Background Virus replication strongly depends on host metabolic machinery and essential cellular factors, in particular, on amino acid profiles. Amino acids play an important role in the pathogenesis of all virus-related infections both as basic substrates for protein synthesis and as regulators in many metabolic pathways, including gene expression. The inhibitory effects of deficiency or excess of these essential elements on virus replication are widely appreciated. Although the same interrelationship between host cellular factors and HIV have been recognized for a long time, the effects of amino acids on HIV-1 RNA replication dynamic is not yet well documented. Our aim was to determine in this pilot study the direct effect of L-lysine amino acid on HIV-1 RNA replication in vitro in HIV-infected patients. Methods A total of 100 HIV-1-infected males without highly active antiretroviral therapy (HAART) were monitored in our center. The patients were in stage A of the disease according to the 1993 Centers for Disease Control (CDC) classification system for HIV-infection. Patients with HIV were enrolled in one stage (A) of the disease with the average amount CD4 lymphocytes in the range of 200–300 cells/µL at the time of sample acquisition. For evaluation of the effects of essential L-lysine amino acid on HIV-1 RNA replication level, we used a model of amino acid-excess system in vitro following incubation of plasma samples for 24 h at 25°C. Quantitative HIV-1 RNA assay was performed using (RT-PCR) reverse-transcriptase polymerase chain reaction (Rotor-Gene Q, QIAGEN, Germany). Results The mean HIV-1 RNA levels were significantly higher in the enriched peripheral blood mononuclear cells plasma samples HIV-infected subjects after 24 h incubation at 25°C temperature than in the plasma samples the same patients studied on the date of blood tests (p 
doi_str_mv 10.1177/2040206614566582
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5890499</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_2040206614566582</sage_id><sourcerecordid>1694960444</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4762-2a28937bdd813de7c196379c428c72def96156f8914138b9afd2d6be741e6e03</originalsourceid><addsrcrecordid>eNqFkV1LHDEYhUNpqav23isJ9KY30-b740YQaXVhURDxNmQz72hkNlmTGcF_09_SX9ZZVm0VSq8C7_ucc5IchA4o-Uqp1t8YEYQRpaiQSknD3qHZZtRsZu_RjFipGs4I20G7td4Rwo3k9iPaYZPCMiVn6HSeun6EFADnDi-a_rHGBNivYsrYh9jinPBwC_hsft1QfHl-jAus-xj8EKdNTL9-PsSh5H30ofN9hU9P5x66-vH96uSsWVyczk-OF00QWrGGeWYs18u2NZS3oAO1imsbBDNBsxY6q6hUnbFUUG6W1ncta9UStKCggPA9dLS1XY_LFbQB0lB879Ylrnx5dNlH93qT4q27yQ9OGkuEtZPBlyeDku9HqINbxRqg732CPFZHtZGMS0LZ_1FlhVVECDGhn9-gd3ksafoIx7jgxEzpm2yypULJtRboXu5Nidv06d72OUkO_37vi-C5wAlotkD1N_An9Z-GvwEj3aWh</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2343088909</pqid></control><display><type>article</type><title>Influence of L-lysine amino acid on the HIV-1 RNA replication in vitro</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Butorov, Evgeny Vlad</creator><creatorcontrib>Butorov, Evgeny Vlad</creatorcontrib><description>Background Virus replication strongly depends on host metabolic machinery and essential cellular factors, in particular, on amino acid profiles. Amino acids play an important role in the pathogenesis of all virus-related infections both as basic substrates for protein synthesis and as regulators in many metabolic pathways, including gene expression. The inhibitory effects of deficiency or excess of these essential elements on virus replication are widely appreciated. Although the same interrelationship between host cellular factors and HIV have been recognized for a long time, the effects of amino acids on HIV-1 RNA replication dynamic is not yet well documented. Our aim was to determine in this pilot study the direct effect of L-lysine amino acid on HIV-1 RNA replication in vitro in HIV-infected patients. Methods A total of 100 HIV-1-infected males without highly active antiretroviral therapy (HAART) were monitored in our center. The patients were in stage A of the disease according to the 1993 Centers for Disease Control (CDC) classification system for HIV-infection. Patients with HIV were enrolled in one stage (A) of the disease with the average amount CD4 lymphocytes in the range of 200–300 cells/µL at the time of sample acquisition. For evaluation of the effects of essential L-lysine amino acid on HIV-1 RNA replication level, we used a model of amino acid-excess system in vitro following incubation of plasma samples for 24 h at 25°C. Quantitative HIV-1 RNA assay was performed using (RT-PCR) reverse-transcriptase polymerase chain reaction (Rotor-Gene Q, QIAGEN, Germany). Results The mean HIV-1 RNA levels were significantly higher in the enriched peripheral blood mononuclear cells plasma samples HIV-infected subjects after 24 h incubation at 25°C temperature than in the plasma samples the same patients studied on the date of blood tests (p &lt; 0.0001). The number of HIV-1 RNA copies increased in 1.5 times. We observed that in plasma of the same HIV-infected patients after adding L-lysine and following incubation in vitro, viral load increased significantly in comparison with standard samples (p &lt; 0.0001). The increased viral load was found in 100/92 (92%) of HIV-infected subjects. The average number of HIV-1 RNA copies in samples had increased by 4.0 times. However, we found no difference in HIV-1 RNA levels after replacement of L-lysine for L-arginine in comparison samples in the same HIV-infected patients. It is obvious that the addition of L-arginine does not increase viral replication in vitro as L-lysine amino acid supplement does. Additionally, no increase in viral load was determined after adding L-lysine and non toxic doses of its inhibitor (L-lysine alpha-oxidase) in plasma samples. Conclusions The results show that L-lysine amino acid excess is characterized by significant increased of HIV-1 RNA copies in enriched peripheral blood mononuclear cells plasma samples of HIV-infected patients. There was evidence for an association between L-lysine supplementation and HIV-1 RNA replication and the level changes of this host essential nutritional element play a key role in the synthesis of the virus proteins and in transcription initiation of the retrovirus life cycle. High intake of L-lysine amino acid may increase the risk of high viral load, subsequent acceleration of immunosuppression and HIV progression. Overall results demonstrate that the simple L-lysine-related model in vitro can be widely used for practical purposes to evaluate HIV-1 RNA replication dynamic, disease prognosis and new approaches in treatment of the patients with human immunodeficiency virus. Although the impact mechanism of L-lysine amino acid on the viral load in the pathogenesis of HIV-infection is at present conjectural and requires further development, the results highlight an interesting target in antiviral therapy, and this statement remains to be proved in further research and clinical trials.</description><identifier>ISSN: 0956-3202</identifier><identifier>EISSN: 2040-2066</identifier><identifier>DOI: 10.1177/2040206614566582</identifier><identifier>PMID: 26149265</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Adult ; Amino Acid Oxidoreductases - pharmacology ; Amino acids ; Antiretroviral drugs ; Antiviral agents ; Arginine ; Arginine - pharmacology ; CD4 antigen ; Clinical trials ; Dietary supplements ; Gene expression ; Highly active antiretroviral therapy ; HIV ; HIV Infections - blood ; HIV-1 - drug effects ; HIV-1 - genetics ; HIV-1 - physiology ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Humans ; Immunosuppression ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - virology ; Life cycles ; Lymphocytes ; Lysine ; Lysine - pharmacology ; Male ; Metabolic pathways ; Metabolism ; Original ; Pathogenesis ; Patients ; Peripheral blood mononuclear cells ; Pilot Projects ; Plasma ; Polymerase chain reaction ; Protein biosynthesis ; Replication ; Ribonucleic acid ; RNA ; RNA, Viral - biosynthesis ; RNA, Viral - blood ; Transcription initiation ; Virus Replication - drug effects ; Young Adult</subject><ispartof>Antiviral chemistry &amp; chemotherapy, 2015-02, Vol.24 (1), p.39-46</ispartof><rights>The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav</rights><rights>The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.</rights><rights>The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the associated terms available at: https://uk.sagepub.com/en-gb/eur/reusing-open-access-and-sage-choice-content</rights><rights>The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav 2015 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4762-2a28937bdd813de7c196379c428c72def96156f8914138b9afd2d6be741e6e03</citedby><cites>FETCH-LOGICAL-c4762-2a28937bdd813de7c196379c428c72def96156f8914138b9afd2d6be741e6e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890499/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890499/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26149265$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Butorov, Evgeny Vlad</creatorcontrib><title>Influence of L-lysine amino acid on the HIV-1 RNA replication in vitro</title><title>Antiviral chemistry &amp; chemotherapy</title><addtitle>Antivir Chem Chemother</addtitle><description>Background Virus replication strongly depends on host metabolic machinery and essential cellular factors, in particular, on amino acid profiles. Amino acids play an important role in the pathogenesis of all virus-related infections both as basic substrates for protein synthesis and as regulators in many metabolic pathways, including gene expression. The inhibitory effects of deficiency or excess of these essential elements on virus replication are widely appreciated. Although the same interrelationship between host cellular factors and HIV have been recognized for a long time, the effects of amino acids on HIV-1 RNA replication dynamic is not yet well documented. Our aim was to determine in this pilot study the direct effect of L-lysine amino acid on HIV-1 RNA replication in vitro in HIV-infected patients. Methods A total of 100 HIV-1-infected males without highly active antiretroviral therapy (HAART) were monitored in our center. The patients were in stage A of the disease according to the 1993 Centers for Disease Control (CDC) classification system for HIV-infection. Patients with HIV were enrolled in one stage (A) of the disease with the average amount CD4 lymphocytes in the range of 200–300 cells/µL at the time of sample acquisition. For evaluation of the effects of essential L-lysine amino acid on HIV-1 RNA replication level, we used a model of amino acid-excess system in vitro following incubation of plasma samples for 24 h at 25°C. Quantitative HIV-1 RNA assay was performed using (RT-PCR) reverse-transcriptase polymerase chain reaction (Rotor-Gene Q, QIAGEN, Germany). Results The mean HIV-1 RNA levels were significantly higher in the enriched peripheral blood mononuclear cells plasma samples HIV-infected subjects after 24 h incubation at 25°C temperature than in the plasma samples the same patients studied on the date of blood tests (p &lt; 0.0001). The number of HIV-1 RNA copies increased in 1.5 times. We observed that in plasma of the same HIV-infected patients after adding L-lysine and following incubation in vitro, viral load increased significantly in comparison with standard samples (p &lt; 0.0001). The increased viral load was found in 100/92 (92%) of HIV-infected subjects. The average number of HIV-1 RNA copies in samples had increased by 4.0 times. However, we found no difference in HIV-1 RNA levels after replacement of L-lysine for L-arginine in comparison samples in the same HIV-infected patients. It is obvious that the addition of L-arginine does not increase viral replication in vitro as L-lysine amino acid supplement does. Additionally, no increase in viral load was determined after adding L-lysine and non toxic doses of its inhibitor (L-lysine alpha-oxidase) in plasma samples. Conclusions The results show that L-lysine amino acid excess is characterized by significant increased of HIV-1 RNA copies in enriched peripheral blood mononuclear cells plasma samples of HIV-infected patients. There was evidence for an association between L-lysine supplementation and HIV-1 RNA replication and the level changes of this host essential nutritional element play a key role in the synthesis of the virus proteins and in transcription initiation of the retrovirus life cycle. High intake of L-lysine amino acid may increase the risk of high viral load, subsequent acceleration of immunosuppression and HIV progression. Overall results demonstrate that the simple L-lysine-related model in vitro can be widely used for practical purposes to evaluate HIV-1 RNA replication dynamic, disease prognosis and new approaches in treatment of the patients with human immunodeficiency virus. Although the impact mechanism of L-lysine amino acid on the viral load in the pathogenesis of HIV-infection is at present conjectural and requires further development, the results highlight an interesting target in antiviral therapy, and this statement remains to be proved in further research and clinical trials.</description><subject>Adult</subject><subject>Amino Acid Oxidoreductases - pharmacology</subject><subject>Amino acids</subject><subject>Antiretroviral drugs</subject><subject>Antiviral agents</subject><subject>Arginine</subject><subject>Arginine - pharmacology</subject><subject>CD4 antigen</subject><subject>Clinical trials</subject><subject>Dietary supplements</subject><subject>Gene expression</subject><subject>Highly active antiretroviral therapy</subject><subject>HIV</subject><subject>HIV Infections - blood</subject><subject>HIV-1 - drug effects</subject><subject>HIV-1 - genetics</subject><subject>HIV-1 - physiology</subject><subject>Human immunodeficiency virus</subject><subject>Human immunodeficiency virus 1</subject><subject>Humans</subject><subject>Immunosuppression</subject><subject>Leukocytes (mononuclear)</subject><subject>Leukocytes, Mononuclear - virology</subject><subject>Life cycles</subject><subject>Lymphocytes</subject><subject>Lysine</subject><subject>Lysine - pharmacology</subject><subject>Male</subject><subject>Metabolic pathways</subject><subject>Metabolism</subject><subject>Original</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Peripheral blood mononuclear cells</subject><subject>Pilot Projects</subject><subject>Plasma</subject><subject>Polymerase chain reaction</subject><subject>Protein biosynthesis</subject><subject>Replication</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Viral - biosynthesis</subject><subject>RNA, Viral - blood</subject><subject>Transcription initiation</subject><subject>Virus Replication - drug effects</subject><subject>Young Adult</subject><issn>0956-3202</issn><issn>2040-2066</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkV1LHDEYhUNpqav23isJ9KY30-b740YQaXVhURDxNmQz72hkNlmTGcF_09_SX9ZZVm0VSq8C7_ucc5IchA4o-Uqp1t8YEYQRpaiQSknD3qHZZtRsZu_RjFipGs4I20G7td4Rwo3k9iPaYZPCMiVn6HSeun6EFADnDi-a_rHGBNivYsrYh9jinPBwC_hsft1QfHl-jAus-xj8EKdNTL9-PsSh5H30ofN9hU9P5x66-vH96uSsWVyczk-OF00QWrGGeWYs18u2NZS3oAO1imsbBDNBsxY6q6hUnbFUUG6W1ncta9UStKCggPA9dLS1XY_LFbQB0lB879Ylrnx5dNlH93qT4q27yQ9OGkuEtZPBlyeDku9HqINbxRqg732CPFZHtZGMS0LZ_1FlhVVECDGhn9-gd3ksafoIx7jgxEzpm2yypULJtRboXu5Nidv06d72OUkO_37vi-C5wAlotkD1N_An9Z-GvwEj3aWh</recordid><startdate>201502</startdate><enddate>201502</enddate><creator>Butorov, Evgeny Vlad</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QR</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7TM</scope><scope>7U9</scope><scope>5PM</scope></search><sort><creationdate>201502</creationdate><title>Influence of L-lysine amino acid on the HIV-1 RNA replication in vitro</title><author>Butorov, Evgeny Vlad</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4762-2a28937bdd813de7c196379c428c72def96156f8914138b9afd2d6be741e6e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Amino Acid Oxidoreductases - pharmacology</topic><topic>Amino acids</topic><topic>Antiretroviral drugs</topic><topic>Antiviral agents</topic><topic>Arginine</topic><topic>Arginine - pharmacology</topic><topic>CD4 antigen</topic><topic>Clinical trials</topic><topic>Dietary supplements</topic><topic>Gene expression</topic><topic>Highly active antiretroviral therapy</topic><topic>HIV</topic><topic>HIV Infections - blood</topic><topic>HIV-1 - drug effects</topic><topic>HIV-1 - genetics</topic><topic>HIV-1 - physiology</topic><topic>Human immunodeficiency virus</topic><topic>Human immunodeficiency virus 1</topic><topic>Humans</topic><topic>Immunosuppression</topic><topic>Leukocytes (mononuclear)</topic><topic>Leukocytes, Mononuclear - virology</topic><topic>Life cycles</topic><topic>Lymphocytes</topic><topic>Lysine</topic><topic>Lysine - pharmacology</topic><topic>Male</topic><topic>Metabolic pathways</topic><topic>Metabolism</topic><topic>Original</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Peripheral blood mononuclear cells</topic><topic>Pilot Projects</topic><topic>Plasma</topic><topic>Polymerase chain reaction</topic><topic>Protein biosynthesis</topic><topic>Replication</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Viral - biosynthesis</topic><topic>RNA, Viral - blood</topic><topic>Transcription initiation</topic><topic>Virus Replication - drug effects</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Butorov, Evgeny Vlad</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antiviral chemistry &amp; chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Butorov, Evgeny Vlad</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of L-lysine amino acid on the HIV-1 RNA replication in vitro</atitle><jtitle>Antiviral chemistry &amp; chemotherapy</jtitle><addtitle>Antivir Chem Chemother</addtitle><date>2015-02</date><risdate>2015</risdate><volume>24</volume><issue>1</issue><spage>39</spage><epage>46</epage><pages>39-46</pages><issn>0956-3202</issn><eissn>2040-2066</eissn><abstract>Background Virus replication strongly depends on host metabolic machinery and essential cellular factors, in particular, on amino acid profiles. Amino acids play an important role in the pathogenesis of all virus-related infections both as basic substrates for protein synthesis and as regulators in many metabolic pathways, including gene expression. The inhibitory effects of deficiency or excess of these essential elements on virus replication are widely appreciated. Although the same interrelationship between host cellular factors and HIV have been recognized for a long time, the effects of amino acids on HIV-1 RNA replication dynamic is not yet well documented. Our aim was to determine in this pilot study the direct effect of L-lysine amino acid on HIV-1 RNA replication in vitro in HIV-infected patients. Methods A total of 100 HIV-1-infected males without highly active antiretroviral therapy (HAART) were monitored in our center. The patients were in stage A of the disease according to the 1993 Centers for Disease Control (CDC) classification system for HIV-infection. Patients with HIV were enrolled in one stage (A) of the disease with the average amount CD4 lymphocytes in the range of 200–300 cells/µL at the time of sample acquisition. For evaluation of the effects of essential L-lysine amino acid on HIV-1 RNA replication level, we used a model of amino acid-excess system in vitro following incubation of plasma samples for 24 h at 25°C. Quantitative HIV-1 RNA assay was performed using (RT-PCR) reverse-transcriptase polymerase chain reaction (Rotor-Gene Q, QIAGEN, Germany). Results The mean HIV-1 RNA levels were significantly higher in the enriched peripheral blood mononuclear cells plasma samples HIV-infected subjects after 24 h incubation at 25°C temperature than in the plasma samples the same patients studied on the date of blood tests (p &lt; 0.0001). The number of HIV-1 RNA copies increased in 1.5 times. We observed that in plasma of the same HIV-infected patients after adding L-lysine and following incubation in vitro, viral load increased significantly in comparison with standard samples (p &lt; 0.0001). The increased viral load was found in 100/92 (92%) of HIV-infected subjects. The average number of HIV-1 RNA copies in samples had increased by 4.0 times. However, we found no difference in HIV-1 RNA levels after replacement of L-lysine for L-arginine in comparison samples in the same HIV-infected patients. It is obvious that the addition of L-arginine does not increase viral replication in vitro as L-lysine amino acid supplement does. Additionally, no increase in viral load was determined after adding L-lysine and non toxic doses of its inhibitor (L-lysine alpha-oxidase) in plasma samples. Conclusions The results show that L-lysine amino acid excess is characterized by significant increased of HIV-1 RNA copies in enriched peripheral blood mononuclear cells plasma samples of HIV-infected patients. There was evidence for an association between L-lysine supplementation and HIV-1 RNA replication and the level changes of this host essential nutritional element play a key role in the synthesis of the virus proteins and in transcription initiation of the retrovirus life cycle. High intake of L-lysine amino acid may increase the risk of high viral load, subsequent acceleration of immunosuppression and HIV progression. Overall results demonstrate that the simple L-lysine-related model in vitro can be widely used for practical purposes to evaluate HIV-1 RNA replication dynamic, disease prognosis and new approaches in treatment of the patients with human immunodeficiency virus. Although the impact mechanism of L-lysine amino acid on the viral load in the pathogenesis of HIV-infection is at present conjectural and requires further development, the results highlight an interesting target in antiviral therapy, and this statement remains to be proved in further research and clinical trials.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>26149265</pmid><doi>10.1177/2040206614566582</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0956-3202
ispartof Antiviral chemistry & chemotherapy, 2015-02, Vol.24 (1), p.39-46
issn 0956-3202
2040-2066
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5890499
source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection
subjects Adult
Amino Acid Oxidoreductases - pharmacology
Amino acids
Antiretroviral drugs
Antiviral agents
Arginine
Arginine - pharmacology
CD4 antigen
Clinical trials
Dietary supplements
Gene expression
Highly active antiretroviral therapy
HIV
HIV Infections - blood
HIV-1 - drug effects
HIV-1 - genetics
HIV-1 - physiology
Human immunodeficiency virus
Human immunodeficiency virus 1
Humans
Immunosuppression
Leukocytes (mononuclear)
Leukocytes, Mononuclear - virology
Life cycles
Lymphocytes
Lysine
Lysine - pharmacology
Male
Metabolic pathways
Metabolism
Original
Pathogenesis
Patients
Peripheral blood mononuclear cells
Pilot Projects
Plasma
Polymerase chain reaction
Protein biosynthesis
Replication
Ribonucleic acid
RNA
RNA, Viral - biosynthesis
RNA, Viral - blood
Transcription initiation
Virus Replication - drug effects
Young Adult
title Influence of L-lysine amino acid on the HIV-1 RNA replication in vitro
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T10%3A38%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Influence%20of%20L-lysine%20amino%20acid%20on%20the%20HIV-1%20RNA%20replication%20in%C2%A0vitro&rft.jtitle=Antiviral%20chemistry%20&%20chemotherapy&rft.au=Butorov,%20Evgeny%20Vlad&rft.date=2015-02&rft.volume=24&rft.issue=1&rft.spage=39&rft.epage=46&rft.pages=39-46&rft.issn=0956-3202&rft.eissn=2040-2066&rft_id=info:doi/10.1177/2040206614566582&rft_dat=%3Cproquest_pubme%3E1694960444%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2343088909&rft_id=info:pmid/26149265&rft_sage_id=10.1177_2040206614566582&rfr_iscdi=true