{"407471":{"#nid":"407471","#data":{"type":"news","title":"Cooperation among viral variants helps Hepatitis C survive immune system attacks","body":[{"value":"\u003Cp\u003EWarring armies use a variety of tactics as they struggle to gain the upper hand. Among their tricks is to attack with a decoy force that occupies the defenders while an unseen force launches a separate attack that the defenders fail to notice.\u003C\/p\u003E\u003Cp\u003EA study published in the May 26 print edition of the journal \u003Cem\u003EProceedings of the National Academy of Sciences\u003C\/em\u003E suggests that the Hepatitis C virus (HCV) may employ similar tactics to distract the body\u0027s natural defenses. After infecting patients, Hepatitis C evolves many variants, among them an \u0022altruistic\u0022 group of viral particles that appears to sacrifice itself to protect other mutants from the body\u0027s immune system.\u003C\/p\u003E\u003Cp\u003EThe findings, reported by researchers from the Georgia Institute of Technology and the Centers for Disease Control and Prevention (CDC), could help guide development of future vaccines and treatments for the virus, which affects an estimated 170 million people in the world. Developing slowly over many years and often without symptoms, Hepatitis C can cause severe liver damage and cancer. There are currently no vaccines for the disease.\u003C\/p\u003E\u003Cp\u003E\u201cThe members of viral populations in Hepatitis C don\u2019t act like separate entities; the different variants work together almost like a team,\u201d said \u003Ca href=\u0022http:\/\/www.math.gatech.edu\/users\/bunimovh\u0022\u003ELeonid Bunimovich\u003C\/a\u003E, a Regent\u2019s Professor in the Georgia Tech \u003Ca href=\u0022http:\/\/www.math.gatech.edu\/\u0022\u003ESchool of Mathematics\u003C\/a\u003E. \u201cThere is a clear separation of responsibilities, including variants we call \u2018altruistic\u2019 because they sacrifice themselves for the good of the whole viral population. These variants seem to draw the immune system attack on themselves.\u201d\u003C\/p\u003E\u003Cp\u003EThe findings resulted from mathematical modeling done by the scientists, who first developed a model for how the virus variants and immune system antibodies interact. They then used the model to analyze and explain data gathered from a group of patients infected with Hepatitis C, some of whom had been followed for as long as 20 years.\u003C\/p\u003E\u003Cp\u003EThe virus evolves differently in each person, producing a mix of genetically-related variants over time, Bunimovich noted. Ultimately, the virus variants and the antibodies form a complex network in which an antibody to one variant can react to another variant \u2013 a phenomenon known as cross-immunoreactivity.\u003C\/p\u003E\u003Cp\u003EBut how do viruses, which lack brains or even neural cells, produce a level of teamwork that\u2019s often difficult for humans to achieve?\u003C\/p\u003E\u003Cp\u003E\u201cThe virus variants do not communicate directly with one another, but in this system of viruses and antibodies, they interact through the antibodies,\u201d explained Bunimovich. \u201cWhen one antibody-producing cell responds to one variant, and then to another, that is a form of interaction that affects both variants. An indirect interaction occurs when the virus variants interact with the same antibody in the network.\u201d\u003C\/p\u003E\u003Cp\u003EUnlike HIV \u2013 to which it is often compared \u2013 Hepatitis C virus doesn\u2019t suppress the body\u2019s immune system. Many scientists believe that the viral infection evolves like an \u201carms race,\u201d with the virus mutating to stay one step ahead of the body\u2019s immune system. Using next-generation gene sequencing data, the research team \u2013 which included regular fellow Pavel Skums and microbiologist Yury Khudyakov from the CDC\u2019s Division of Viral Hepatitis \u2013 analyzed viral populations in detail. The scientists studied the genetic compositions of the populations, and even saw evolution in blood samples taken from the same persons over time.\u003C\/p\u003E\u003Cp\u003EThe populations of variants rose and fell, some remaining in small numbers and others reappearing after they had been seemingly wiped out by the immune system. At late stages of the persistent infection development, the evolution of new variations almost stopped, though the immune system remained strong. The \u201carms race\u201d theory fails to explain these observations, Bunimovich said.\u003C\/p\u003E\u003Cp\u003EUsing their model to track both variants and antibodies, the researchers found that certain variants were drawing the immune system response on themselves to protect others. They called this newly-observed phenomenon \u201cantigenic cooperation.\u201d The antibodies suppressed only the altruistic variants, leaving other viral members of the network unharmed.\u003C\/p\u003E\u003Cp\u003E\u201cThe altruistic variants allow the antibodies to attack them, thereby sacrificing themselves, so other variants can survive,\u201d said Skums, the paper\u2019s first author. \u201cThe altruistic variants fool the immune system, rendering the immune system response to other variants ineffective. In essence, the surviving variants use the altruistic (sacrificing) variants as an umbrella to protect themselves.\u201d\u003C\/p\u003E\u003Cp\u003EThe researchers were surprised by the sophisticated behavior, which occurs because the viral variants are part of the complex interconnected network \u2013 a social network not unlike the ones created in such environments as Facebook.\u003C\/p\u003E\u003Cp\u003E\u201cEven such simple organisms as viruses can organize into a network,\u201d Skums explained. \u201cBecause they are part of a network, they can develop this kind of complex behavior, fighting the immune system through team efforts.\u201d\u003C\/p\u003E\u003Cp\u003EThe findings, if supported by additional research, could alter the strategy for developing vaccines for Hepatitis C. Both vaccines and treatment would have to take into account how the virus evolves differently in individuals. The researchers also hope to examine the activity of other viruses to see if this complex interaction may also be found in other viral networks, Bunimovich said.\u003C\/p\u003E\u003Cp\u003EFor the researchers, mathematics allowed them to see patterns that might otherwise have remained hidden in the complex patient data.\u003C\/p\u003E\u003Cp\u003E\u201cNow that we see this from the mathematical model, everything makes sense,\u201d said Skums. \u201cWhen you look at this mathematically, you can see the whole picture.\u201d\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECITATION\u003C\/strong\u003E: \u201cAntigenic cooperation among intrahost HCV variants organized into a complex network of cross-immunoreactivity,\u201d (Proceedings of the National Academy of Sciences, published ahead of print May 4, 2015). \u003Ca href=\u0022http:\/\/www.dx.doi.org\/10.1073\/pnas.1422942112\u0022\u003Ehttp:\/\/www.dx.doi.org\/10.1073\/pnas.1422942112\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EResearch News\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003EGeorgia Institute of Technology\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003E177 North Avenue, Atlanta, GA 30332-0181 USA\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EMedia Relations Contacts\u003C\/strong\u003E: John Toon (404-894-6986) (\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E) or Brett Israel (404-385-1900) (\u003Ca href=\u0022mailto:brett.israel@comm.gatech.edu\u0022\u003Ebrett.israel@comm.gatech.edu\u003C\/a\u003E).\u003Cbr \/\u003E\u003Cstrong\u003EWriter\u003C\/strong\u003E: John Toon\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EWarring armies use a variety of tactics, including use of a decoy force that occupies the defenders while an unseen force launches a separate attack that the defenders fail to notice. A new study suggests that the Hepatitis C virus (HCV) may employ similar tactics to distract the body\u0027s natural defenses.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"A new study suggests that the Hepatitis C virus may use decoy viral variants to distract the body\u0027s natural defenses."}],"uid":"27303","created_gmt":"2015-05-26 21:47:18","changed_gmt":"2016-10-08 03:18:21","author":"John Toon","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2015-05-27T00:00:00-04:00","iso_date":"2015-05-27T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"407451":{"id":"407451","type":"image","title":"Viral cooperation","body":null,"created":"1449254168","gmt_created":"2015-12-04 18:36:08","changed":"1475895132","gmt_changed":"2016-10-08 02:52:12","alt":"Viral cooperation","file":{"fid":"202146","name":"virus-collaboration.jpg","image_path":"\/sites\/default\/files\/images\/virus-collaboration_0.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/virus-collaboration_0.jpg","mime":"image\/jpeg","size":1195573,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/virus-collaboration_0.jpg?itok=BS9x_u53"}},"407461":{"id":"407461","type":"image","title":"Viral cooperation2","body":null,"created":"1449254168","gmt_created":"2015-12-04 18:36:08","changed":"1475895132","gmt_changed":"2016-10-08 02:52:12","alt":"Viral cooperation2","file":{"fid":"202147","name":"virus-network.jpg","image_path":"\/sites\/default\/files\/images\/virus-network_0.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/virus-network_0.jpg","mime":"image\/jpeg","size":636463,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/virus-network_0.jpg?itok=IfFq3z_d"}}},"media_ids":["407451","407461"],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"146","name":"Life Sciences and Biology"},{"id":"135","name":"Research"}],"keywords":[{"id":"123","name":"CDC"},{"id":"126991","name":"hepatitis c"},{"id":"9316","name":"immune system"},{"id":"127011","name":"Leonid Bunimovich"},{"id":"763","name":"vaccine"},{"id":"127001","name":"viral variant"},{"id":"4292","name":"virus"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"},{"id":"39431","name":"Data Engineering and Science"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EJohn Toon\u003C\/p\u003E\u003Cp\u003EResearch News\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E404-894-6986\u003C\/p\u003E","format":"limited_html"}],"email":["jtoon@gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}