Price AM, Luftig MA. Int J Rheum Dis (2015) 18:70. doi: 10.1111/1756-185X.12298, 163. EBV infection and the associated immune response results in production of antibodies (seroconversion), which occurs mainly during the first years of life, but may also happen during adolescence or later in life. Virus particles in cultured lymphoblasts from Burkitts lymphoma. Emerging viral infections in rheumatic diseases. Chin J Cancer (2014) 33:545. doi: 10.5732/cjc.014.10168, 29. Rev Med Virol (2015) 20152:71. doi: 10.1002/rmv.1816, 83. As immune cells called B lymphocytes get activated to fight viral infections, virus proteins can bind onto the human genome and increase the risk of autoimmune diseases. Neuroscientist (2011) 17:351. doi: 10.1177/1073858410381531, 85. Kwok H, Chan KW, Chan KH, Chiang AK. Currently, Epstein-Barr virus is accepted as a causal agent only for multiple sclerosis. Epstein-Barr infects B cellsa type of white blood cell in the immune system. The Essential Role of Epstein-Barr Virus in the Pathogenesis of Multiple Sclerosis. Other genes have also been associated with the development of lupus. However, all these studies are hampered by a relative scarcity of seronegative persons. 13 Articles, This article is part of the Research Topic, https://doi.org/10.3389/fimmu.2020.587380, Creative Commons Attribution License (CC BY). Similar to chickenpox or oral herpes virus, it remains with an infected person throughout life. Content on this website is not considered medical advice. Maibom-Thomsen SL, Trier NH, Holm BE, Hansen KB, Rasmussen MI, Chailyan A, et al. Esposito S, Bosis S, Semino M, Rigante D. Infections and systemic lupus erythematosus. Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, et al. Xiao J, Palefsky JM, Herrera R, Berline J, Tugizov SM. The new knowledge brings help and hope to those who suffer from these chronic illnesses. Annu Rev Pathol (2019) 14:29. doi: 10.1146/annurev-pathmechdis-012418-013023, 101. The circular double-stranded genome of EBV is approximately 172 kilobases, with more than hundred genes coding for approximately 85 proteins (Table 1) and approximately 50 non-coding RNAs (812). Maliska M. The role of Epstein-Barr virus infection in primary Sjgrens syndrome. Alleles of many genes are known to contribute to RA, notable HLA-DRB1 alleles containing shared epitope (SE) motives, but many other genes affecting the immune system and in particular lymphocytes have an impact (108, 110, 117). Yoon SI, Jones BC, Logsdon NJ, Harris BD, Kuruganti S, Walter MR. Epstein-Barr virus IL-10 engages IL-10R1 by a two-step mechanism leading to altered signaling properties. Int J Biol Sci (2018) 5:565. doi: 10.7150/ijbs.24562, 104. The Epstein-Barr virus (EBV) typically infects individuals during early life, remaining within the body indefinitely without triggering noticeable symptoms. Ana Pena, PhD Nat Rev Microbiol (2019) 17:691. doi: 10.1038/s41579-019-0249-7, 53. The new study, however, does more than confirm an association; it shows a component of possible mechanism: the binding of EBNA2 to specific genes. As a result, trimeric gB changes conformation and promotes fusion of the viral membrane with the endosome membrane, thus releasing the virus to the cytoplasm (Figures 13) (20, 26, 27). Future studies should focus on interaction of EBV proteins and non-coding RNAs with host molecules and on the role of other viruses in relation to EBV infection. Lupus is a "snowflake" condition, meaning that . Severe acute respiratory syndrome coronavirus 2 (SARSCoV2) is a novel viral agent that can cause a life-threatening respiratory disorder named coronavirus disease 2019 (COVID19). Int Rev Immunol (2014) 4:330. doi: 10.3109/08830185.2013.863305, 159. Appointments Contact Us Causes Complications Prevention Overview Infectious mononucleosis (mono) is often called the kissing disease. Epstein-Barr (EBV) is a virus that causes mononucleosis . Farina A, Feederle R, Raffa S, Gonnella R, Santarelli R, Frati L, et al. This information is not designed to replace a physicians independent judgment about the appropriateness or risks of a procedure for a given patient. MHC class II and III represent two families of genes known to be associated with lupus. The first EBV variants identified were type 1 (type A) and type 2 (type B). 73. Association between SARSCoV2 and SLE is not clear. Human gammaherpesvirus immune evasion strategies. Lupus.net does not provide medical advice, diagnosis or treatment. SLE has been described as an immune complex disease, since it is often associated with decreased levels of complement components (140). EBV, which is also called HHV4, belongs to the Gammaherpesviridae, genus Lymphocryptovirus (6, 7). See additional information. This attack causes inflammation, and in some cases permanent tissue damage, which can be . Cambridge, UK: Cambridge University Press (2007). Assessment of disease activity in Systemic Lupus Erythematosus: Lights and shadows. And does that mean you can get mono, It can take anywhere from 4 to 6 weeks after exposure for mono symptoms to appear. Epstein-Barr virus-encoded BARF1 protein is a decoy receptor or macrophage colony stimulating factor and interferes with macrophage differentiation and activation. 98. While type 1 (B95-8, GD1, and Akata) is the main EBV type prevalent worldwide, type 2 (AG876 and P3HR-1) is as abundant as type 1 in sub-Saharan Africa (13). They looked at genes activated in immune cells called B lymphocytes that are involved in fighting viral infections. The presence of heterophile antibodies has a high specificity for infectious mononucleosis. While researchers are confident that lupus is caused by both genes and environmental triggers, they cannot determine which factor sets the disease in motion or how precisely these two elements interact. To show that Epstein-Barr causes M.S., or any other condition that . While there's no cure . Some people may only feel fatigued. Considering that EBV can cause autoimmune responses, some of the steps used to manage lupus symptoms can also be used to manage the symptoms of EBV infections. The presence of DNA Abs and other ANAs would seem to be compatible with infection by a DNA virus in combination with inefficient removal of apoptotic and necrotic material. They do this by "turning on and off" genes, controlling when that gene creates a product such as a protein. Annually, 10% to 20% of EBV-naive persons become infected, and 30% to 50% develop IM . IM itself is a prolonged state of fever, swollen lymph nodes, fatigue, malaise and various other symptoms. The seven diseases linked to theEBNA2 protein are lupus, multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory bowel disease, celiac disease, and Type 1 diabetes. There are no widely accepted criteria (rules) for diagnosis. This in turn mounts an increased immune response against EBV, neutralizing infected cells and forcing the virus into latency again. Corrections? But thats not to say that all cases of mono are STIs. Salek-Ardakani S, Arrand JR, Mackett M. Epstein-Barr virus encoded interleukin-10 inhibits HLA-class I, ICAM-1, and B7 expression on human monocytes: implications for immune evasion by EBV. It is the cause of mononucleosis, and is also associated with some forms of cancer and other conditions. There are also dozens of gene variants that increase a persons risk of developing autoimmune diseases. The gH/gL interaction with integrins is mediated by a KGD motif on gH, and the interaction between gH/gL and EphA2 occurs through the receptors ligand binding and fibronectin type III repeats and is mediated by the gP42 binding site on gH. Heres what you need to, Infectious mononucleosis, or mono, is commonly referred to as the kissing disease because its spread through saliva. The effect of cigarette smoking on the clinical and serological phenotypes of polymyositis and dermatomyositis. Transl Res (2006) 6:281. doi: 10.1016/j.trsl.2006.07.003, 131. Changes in the result of antinuclear antibody immunofluorescence assay on HEp-2 cells reflect disease activity status in systemic lupus erythematosus. The viral envelope derived from the host cell (Figure 2) offers substantial protection to the enclosed viral particle by mimicking a host extracellular vesicle. Epstein-Barr virus large tegument protein BPLF1 contributes to innate immune evasion through interference with toll-like receptor signaling. Genetic factors influencing EBV control are in principle all genes of the immune system. Infection of adolescents can . The relationships between cancer and autoimmune rheumatic diseases. Developing new drug treatments or vaccines will take years more of further research. Clin Microbiol Rev (2011) 1:193. doi: 10.1128/CMR.00044-10, 24. Epstein-Barr Virus (EBV) is a lymphotropic herpes virus and the causative agent of infectious mononucleosis (IM) (14). The team analyzed genomic data with a new computer algorithm they created called RELIshort for Regulatory Element Locus Intersection. entry, which in RA seems to be facilitated by SE-containing HLA alleles. In: Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, et al., editors. Linde A. Lupus patients have also been shown to have elevated Epstein-Barr virus loads in their blood. FEMS Microbiol Rev (2019) 43:674. doi: 10.1093/femsre/fuz023, 33. Both processes release virions and viral tegument proteins into the cytoplasm. Clinical features and laboratory findings in children hospitalized with acute Epstein-Barr virus infection: a crosssectional study in a tertiary care hospital. Chen J, Longnecker R. Epithelial cell infection by Epstein-Barr virus. Curr Opin Rheumatol (2010) 1:72. doi: 10.1097/BOR.0b013e328333b9f5, 181. The American College of Rheumatology (ACR) and the Centers for Disease Control and Prevention (CDC) recommend that people with lupus who meet the age requirements receive a series of COVID-19 vaccines. Often, mono also comes with a rash, a sore throat, and swelling of the liver, lymph nodes, and spleen.1,2,5, While many people with lupus develop a rash as well, the rash appears on the face in a distinct shape. The link between the Epstein-Barr virus and lupus has been shown by multiple research groups. Get more resources at VeteransCrisisLine.net. Clin Exp Med (2019) 1:23. doi: 10.1007/s10238-018-0535-0, 149. Figure 1 Schematic presentation of Epstein-Barr virus. By providing your email address, you are agreeing to our Privacy Policy and Terms of Use. Only about 25 percent of kids and young adults exposed to EBV come down with infectious mononucleosis (mono). Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. It can cause many different symptoms, including fever, fatigue, rashes, body aches, and confusion. The SADs include the relatively common rheumatoid arthritis (RA) and the more rare conditions Sjgrens syndrome (SS), systemic lupus erythematosus (SLE), systemic scleroderma (SSc), and others (Table 2) (106, 107). Technically, yes, mono can be considered a sexually transmitted infection (STI). Lupus is a chronic autoimmune disease affecting about 1.5 million Americans, with an estimated 16,000 newly diagnosed each year. J Infect Dis (1999) 180:496. doi: 10.1086/314883, 84. PLoS Pathog (2016) 12:e1005550. Parenting is one of the most complex and challenging jobs you'll face in your lifetime -- but also the most rewarding. The virus has changed and is now easier to catch and transmit, even for people who are vaccinated, but it is much less likely to get it or have . Scientists have known for decades that EBV, which causes an infectious disease named mononucleosis or "kissing disease," is also linked to several autoimmune disorders, including multiple sclerosis and rheumatoid arthritis. Your doctor can order a test for EBV antibodies to see if you had the infection. Together, we discuss the importance of testing for, identifying, and treating the infections that exacerbate symptoms of autoimmunity. Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to G-quadruplexes of EBNA1 mRNA. Association of Smoking and Obesity on the Risk of Developing Primary Sjgren Syndrome: A Population-based Cohort Study. Learn more about how we maintain editorial integrity. The blood serum of individuals with mononucleosis contains an antibody (referred to as a sheep cell or heterophil agglutinin) that is characteristic of the disease, but antibodies against EBV itself are more-specific markers of the infection. gH/gL supercomplexes at early stages of herpesvirus entry. But in some cases it can lead to, Reasons for this link are not known, but t. he new study provided an important clue. Gaipl US, Voll RE, Sheriff A, Franz S, Kalden JR, Herrmann M. Impaired clearance of dying cells in systemic lupus erythematosus. Wang HB, Zhang H, Zhang JP, Li Y, Zhao B, Feng GK, et al. Epstein-Barr virus persistence and infection of autoreactive plasma cells in synovial lymphoid structures in rheumatoid arthritis. Infections as a cause of autoimmune rheumatic diseases. There is no specific therapy. Science (1990) 248:1230. Drinking plenty of water and eating a healthy diet is also essential. 3 W Garden St Treatments can ease symptoms until the illness goes away on its own. In principle, the viral envelope may contain all host-derived membrane proteins relevant for disguise and immune evasion (e.g. Infectious disease agents such as the Epstein-Barr Virus (EBV, which causes mononucleosis or mono), herpes zoster virus (the virus that causes shingles), and cytomegalovirus have also been implicated. Trends Mol Med (2020) 26:296. doi: 10.1016/j.molmed.2019.11.003. The structural and mechanistic basis of B cell entry has been elucidated in much detail by solving the structures of gB, gP42, complexes of gH/gL, gP42/MHC-II (human leukocyte antigen (HLA)-DR1) and of gH/gL/gP42/MHC-II in pre- and post-fusion conformations (20, 38, 39). Please refer to the appropriate style manual or other sources if you have any questions. Mononucleosis, which causes weeks of extreme fatigue, is the most common illness caused by EBV. Pol J Microbiol (2018) 1:81. doi: 10.5604/01.3001.0010.6287, 87. A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates. Now, using genomic methods that were not available 10 years ago, it appears that components made by the virus interact with human DNA in the places where the genetic risk of disease is increased, John B. Harley, MD, PhD, director of the Center for Autoimmune Genomics and Etiology, orCAGE, at Cincinnati Childrens Hospital and the studys first author, said in a press release. Furthermore, EBV has been demonstrated to be present in the synovium of RA patients (115, 125, 126). For now, doctors prescribe existing drugs to treat lupus. Liebermann PM, Hu J, Renne R. Maintenance and replication during latency. An effective vaccine would prevent disease altogether for at least some patients, even if the virus is not the only possible cause. Arthritis Res Ther (2015) 17:274. doi: 10.1186/s13075-015-0755-6, 120. If this unexpected relationship between the Epstein-Barr virus and autoimmune diseases in fact proves to be the root cause for at least some of the patients with these diseases, then a vaccine could be developed. Lupus Center News Ive helped thousands of patients at my clinic and tens of thousands more around the world overcome their autoimmune conditions by addressing underlying infections such as EBV. The etiology has been suggested to involve molecular mimicry between EBV EBNA1 and cellular Ro 60, and/or bystander activation (154, 155). Many college students know it as the virus that causes the kissing disease, or mono (mononucleosis.). Int J Rheum Dis (2020) 6:723. doi: 10.1111/1756-185X.13839, 128. "These are very clearly newly acquiredno question about it," he explains, pointing to one . Philos Trans R Soc Lond B Biol Sci (2001) 1408:461. doi: 10.1098/rstb.2000.0783, 25. April 25, 2018. Conventional medical testing includes both a complete EBV acute panel and a chronic infection panel to ensure reliable results.9. BMC Infect Dis (2017) 1:323. doi: 10.1186/s12879-017-2412-y, 89. doi: 10.1371/journal.pone.0208957, 116. sunlight/VitD has been proposed to protect against autoimmunity by increasing the number of CD8+ T cells available to control EBV infection (84). Federal government websites often end in .gov or .mil. Human inborn errors of immunity to herpes viruses. A Genome-Wide Epstein-Barr Virus Polyadenylation Map and Its Antisense RNA to EBNA. Epstein Barr Virus Interleukin 10 Suppresses Anti-inflammatory Phenotype in Human Monocytes. I have also seen the . RNA Biol (2014) 1:10. doi: 10.4161/rna.27488, 11. BFRF1 of Epstein-Barr virus is essential for efficient primary viral envelopment and egress. The HLA profiles of mixed connective tissue disease differ distinctly from the profiles of clinically related connective tissue diseases. This initiates transcription of viral genes in a sequence of immediate-early (iE) genes, coding for regulatory alfa-proteins, early genes, coding for catalytic beta-proteins, and late (L) genes, coding for structural gamma proteins. F1000Res (2015) 4:939. doi: 10.12688/f1000research.6875.1, 144. All authors contributed to the article and approved the submitted version. J Autoimmun (2020) 110:102392. doi: 10.1016/j.jaut.2019.102392, 112. Parks CG, de Souza Espindola Santos A, Barbhaiya M, Costenbader KH. The Epstein-Barr virus BMRF-2 protein facilitates virus attachment to oral epithelial cells. Scherer HU, Hupl T, Burmester GR. Eur J Dermatol (2019) 1:21. doi: 10.1684/ejd.2018.3490, 106. in response to antigen stimulation of memory B cells, resulting in lytic production of virions upon expression of an ordered sequence of viral genes (5557). April 18, 2018 A new study by Lupus Research Alliance-funded researcher Dr. Matthew Weirauch of the Cincinnati Children's Hospital Medical Center in Ohio and colleagues might explain how a common virus that causes mononucleosis also boosts the risk for lupus.