INFECTIOUS MONONUCLEOSIS:
"The Kissing Disease"
Editor's Note: Lucas F. ('15) details how mono, one of the diseases that ravaged Packer, is contagious and how it is spread.
Introduction
Infectious mononucleosis (IM), commonly known as “mono,” is a viral infection especially prevalent in adolescents and young adults. The primary cause of this infection is a virus of the herpes family called, the Epstein-Barr virus (EBV). It is not particularly contagious, hard to believe given the recent outbreak at Packer, as it spreads solely through salvia. There are many symptoms of IM, making it close to impossible to diagnose without blood work, but the primary signs are: fatigue, swollen lymph nodes, sore throat, and fever. Each of these symptoms last for varying lengths and is also dependent on the severity of the infection. However symptoms generally last for at least 2-3 weeks and after a couple months the malaise usually dissipates. And as mentioned earlier, EPV is almost always the cause of these symptoms.
Structure of Epstein-Barr Virus (EBV)
EPV is a DNA virus with a structure similar to that of other herpesviridae. The most important components for infection are the glycoproteins protruding from the envelope. These are the same type of membrane proteins that make up antibodies and the major histocompatibility complex (MHC). They are vital for the EPV to enter and infect cells. The cells, which EBV typically infects, are B cells and epithelial cells.
EPV Replication: Lytic Cycle
There are two ways in which EPV spreads and ultimately remains in your body: the lytic cycle and latency. The lytic cycle is a common mode of replication for viruses where the virus inserts its genetic material into a cell (or simply inserts the entire virus as is the case with EPV), reproduces itself within that cell without attaching to cell’s original DNA and ultimately bursts the host cell apart with the exit of all the newly created viruses. In EPV’s case however it is slightly different. The major difference being, instead of bursting apart the host cell (either B or epithelial cells), it “sheds” the created viruses, keeping the host alive. This allows for the original host cell to continue producing viruses in the system once infected, and greatly increases the spread of the virus throughout the body.
EPV Infection: Latency
Latency is a mode of persistence that is less common among viruses and allows EPV to activate in a more controlled manner rather than immediately after being introduced to the host. Once injected into the cell, the genetic material of EPV remains as an episome in the nucleus. Only a fraction of the genes in this episome are expressed at a time and exhibit three different latency programs. These programs (Latency I/II/III) are patterns of protein production where each latency program expresses different genes and leads to the production of different proteins. Each latency program also has a different affect on the host cell. The epithelial cells generally are the first cells to be infected. And while they have only shown one Latency program, they are crucial for the spread of the disease throughout the body and particularly to other people. The saliva is cause of EPV’s spread because of the infection of oral epithelial cells. In B cells, it is arguably a lot more interesting, not only are all Latency programs possible but lymphocyte infection is key to dodging the immune system. Also, only in B cells is it possible for an infected cell to go from a latent state to lytic reproduction.
Manipulation of B Cell Lymphocytes
Diamonds are forever and so is EPV. Once a person has been infected with the virus, they will always carry it with them. An infected B lymphocyte goes through three stages based on the three Latency programs. First the B cell becomes immortal by turning into a lymphoblast, an activated form of the lymphocyte where it begins to split and duplicate. Before the host has established an immunity against EBV, these lymphoblasts accelerate the spread of the virus. Once the immune systems detects and is able to classify EBV, the virus restricts its own gene expression going into Latency I and II. Through these latency programs, EBV turns the lymphoblast into a memory B cell that is capable of duplicating the EBV episome after mitosis. Essentially meaning that once an immune response is established, the virus is able to live inactive and permanently undetected within the host’s own lymphocytes.
Immune Response to EBV: Cytotoxic T Lymphocytes (CTL)
The primary and most effective immune response against EBV is cytotoxic T lymphocytes, also known as killer T cells. These T cells are designed to kill cancerous and virally infected cells. While EBV has no defense mechanism to fight back against these CTLs, it does seem to be able to resist antigen recognition, allowing the virus to be active for such an extended period of time. However it is important to remember that IM, and therefore also EBV, is a self-limiting illness. There is no treatment for IM other than rest and perhaps some medication to help alleviate the symptoms. The virus will eventually be caught and killed by these cytotoxic T lymphocytes, it is inevitable and only a matter of time. However, what is especially fascinating with this virus is its capability to integrate into the immune system. As mentioned earlier, the episome containing the viral genetic material will remain latent in the host’s memory B cells. So while this virus’ danger is essentially neutralized, its legacy remains forever silent in almost every human on this planet.
Vaccines
While 95% of adults have the EPV, there is still no vaccine available. Currently the ones in trial phases work by releasing antibodies programmed to target specific glycoproteins to prevent EBV cell infection. So far these vaccines have been somewhat successful where after testing 10 EBV positive children 6 of 9 became uninfected after being treated with this “vaccination.” Nevertheless, all the vaccines for EPV are still in testing phases and it is unknown how long it will take for it to be both highly effective and ready for public release. In the meantime, one should be even more careful to not share cups, toothbrushes, or even kisses with those who are sick. And if you do contract IM, try to rest easy knowing your body will kill it eventually. Eventually the virus will rest in your memory and the memory of your B cells.
Infectious mononucleosis (IM), commonly known as “mono,” is a viral infection especially prevalent in adolescents and young adults. The primary cause of this infection is a virus of the herpes family called, the Epstein-Barr virus (EBV). It is not particularly contagious, hard to believe given the recent outbreak at Packer, as it spreads solely through salvia. There are many symptoms of IM, making it close to impossible to diagnose without blood work, but the primary signs are: fatigue, swollen lymph nodes, sore throat, and fever. Each of these symptoms last for varying lengths and is also dependent on the severity of the infection. However symptoms generally last for at least 2-3 weeks and after a couple months the malaise usually dissipates. And as mentioned earlier, EPV is almost always the cause of these symptoms.
Structure of Epstein-Barr Virus (EBV)
EPV is a DNA virus with a structure similar to that of other herpesviridae. The most important components for infection are the glycoproteins protruding from the envelope. These are the same type of membrane proteins that make up antibodies and the major histocompatibility complex (MHC). They are vital for the EPV to enter and infect cells. The cells, which EBV typically infects, are B cells and epithelial cells.
EPV Replication: Lytic Cycle
There are two ways in which EPV spreads and ultimately remains in your body: the lytic cycle and latency. The lytic cycle is a common mode of replication for viruses where the virus inserts its genetic material into a cell (or simply inserts the entire virus as is the case with EPV), reproduces itself within that cell without attaching to cell’s original DNA and ultimately bursts the host cell apart with the exit of all the newly created viruses. In EPV’s case however it is slightly different. The major difference being, instead of bursting apart the host cell (either B or epithelial cells), it “sheds” the created viruses, keeping the host alive. This allows for the original host cell to continue producing viruses in the system once infected, and greatly increases the spread of the virus throughout the body.
EPV Infection: Latency
Latency is a mode of persistence that is less common among viruses and allows EPV to activate in a more controlled manner rather than immediately after being introduced to the host. Once injected into the cell, the genetic material of EPV remains as an episome in the nucleus. Only a fraction of the genes in this episome are expressed at a time and exhibit three different latency programs. These programs (Latency I/II/III) are patterns of protein production where each latency program expresses different genes and leads to the production of different proteins. Each latency program also has a different affect on the host cell. The epithelial cells generally are the first cells to be infected. And while they have only shown one Latency program, they are crucial for the spread of the disease throughout the body and particularly to other people. The saliva is cause of EPV’s spread because of the infection of oral epithelial cells. In B cells, it is arguably a lot more interesting, not only are all Latency programs possible but lymphocyte infection is key to dodging the immune system. Also, only in B cells is it possible for an infected cell to go from a latent state to lytic reproduction.
Manipulation of B Cell Lymphocytes
Diamonds are forever and so is EPV. Once a person has been infected with the virus, they will always carry it with them. An infected B lymphocyte goes through three stages based on the three Latency programs. First the B cell becomes immortal by turning into a lymphoblast, an activated form of the lymphocyte where it begins to split and duplicate. Before the host has established an immunity against EBV, these lymphoblasts accelerate the spread of the virus. Once the immune systems detects and is able to classify EBV, the virus restricts its own gene expression going into Latency I and II. Through these latency programs, EBV turns the lymphoblast into a memory B cell that is capable of duplicating the EBV episome after mitosis. Essentially meaning that once an immune response is established, the virus is able to live inactive and permanently undetected within the host’s own lymphocytes.
Immune Response to EBV: Cytotoxic T Lymphocytes (CTL)
The primary and most effective immune response against EBV is cytotoxic T lymphocytes, also known as killer T cells. These T cells are designed to kill cancerous and virally infected cells. While EBV has no defense mechanism to fight back against these CTLs, it does seem to be able to resist antigen recognition, allowing the virus to be active for such an extended period of time. However it is important to remember that IM, and therefore also EBV, is a self-limiting illness. There is no treatment for IM other than rest and perhaps some medication to help alleviate the symptoms. The virus will eventually be caught and killed by these cytotoxic T lymphocytes, it is inevitable and only a matter of time. However, what is especially fascinating with this virus is its capability to integrate into the immune system. As mentioned earlier, the episome containing the viral genetic material will remain latent in the host’s memory B cells. So while this virus’ danger is essentially neutralized, its legacy remains forever silent in almost every human on this planet.
Vaccines
While 95% of adults have the EPV, there is still no vaccine available. Currently the ones in trial phases work by releasing antibodies programmed to target specific glycoproteins to prevent EBV cell infection. So far these vaccines have been somewhat successful where after testing 10 EBV positive children 6 of 9 became uninfected after being treated with this “vaccination.” Nevertheless, all the vaccines for EPV are still in testing phases and it is unknown how long it will take for it to be both highly effective and ready for public release. In the meantime, one should be even more careful to not share cups, toothbrushes, or even kisses with those who are sick. And if you do contract IM, try to rest easy knowing your body will kill it eventually. Eventually the virus will rest in your memory and the memory of your B cells.
Glossary
|
Glycoprotein: membrane proteins that have carbohydrates attached to them
Epithelial cells: these are the cells that make up the lining of our organs Episome: a plasmid of autonomous extra-chromosomal DNA |
Latency programs: these programs (Latency I/II/III) are patterns of protein production where each latency program expresses different genes and leads to the production of different proteins
Lymphoblast: an activated form of the lymphocyte that has stimulated by antigen and begins to split and duplicate |
About Epstein-Barr Virus (EBV). (2014, January 6). Retrieved March 3, 2015, from http://www.cdc.gov/epstein-barr/about-ebv.html
Ben Taylor (Creator). (2010). Viral Tegument [Digital Image], Retrieved March 3, 2015, (http://upload.wikimedia.org/wikipedia/commons/b/bb/Viral_Tegument.svg)
Campbell, N., & Reece, J. (2002). Biology (9th ed., p. 383). San Francisco: Benjamin
Campbell, N., & Reece, J. (2002). Biology (9th ed., p. 856). San Francisco: Benjamin
Cohen, J. (2014). Epstein–Barr Virus Vaccines. Clinical & Translational Immunology, 4-
Elliott, S., Suhrbier, A., Miles, J., Lawrence, G., Pye, S., Le, T., ... Bharadwaj, M. (2008). Phase I Trial of a CD8 T-Cell Peptide Epitope-Based Vaccine for Infectious Mononucleosis. Journal of Virology, 1448-1457.
Epstein-Barr Virus. (n.d.). Retrieved March 3, 2015, from http://www.bio.davidson.edu/courses/Immunology/Students/spring2000/christian/restrict
Infectious Mononucleosis. (n.d.). Retrieved March 2, 2015, from http://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/mono.htm
Moss, D., Burrows, S., Silins, S., Misko, I., & Khanna, R. (2001). The Immunology of Epstein-Barr Virus Infection. The Royal Society, 356(1408), 475-488.
Odumade, O., Hogquist, K., & Balfour, H. (n.d.). Progress and Problems in Understanding and Managing Primary Epstein-Barr Virus Infections. Clinical Microbiology Reviews, 193-209.
Robertson, E. (2010). Epstein-Barr virus: Latency and transformation. Wymondham, Norfolk, UK: Caister Academic Press.
Taylor, G., Long, H., Brooks, J., Rickinson, A., & Hislop, A. (2015). The Immunology of Epstein-Barr Virus–Induced Disease. Annual Review of Immunology, 33.
Ben Taylor (Creator). (2010). Viral Tegument [Digital Image], Retrieved March 3, 2015, (http://upload.wikimedia.org/wikipedia/commons/b/bb/Viral_Tegument.svg)
Campbell, N., & Reece, J. (2002). Biology (9th ed., p. 383). San Francisco: Benjamin
Campbell, N., & Reece, J. (2002). Biology (9th ed., p. 856). San Francisco: Benjamin
Cohen, J. (2014). Epstein–Barr Virus Vaccines. Clinical & Translational Immunology, 4-
Elliott, S., Suhrbier, A., Miles, J., Lawrence, G., Pye, S., Le, T., ... Bharadwaj, M. (2008). Phase I Trial of a CD8 T-Cell Peptide Epitope-Based Vaccine for Infectious Mononucleosis. Journal of Virology, 1448-1457.
Epstein-Barr Virus. (n.d.). Retrieved March 3, 2015, from http://www.bio.davidson.edu/courses/Immunology/Students/spring2000/christian/restrict
Infectious Mononucleosis. (n.d.). Retrieved March 2, 2015, from http://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/mono.htm
Moss, D., Burrows, S., Silins, S., Misko, I., & Khanna, R. (2001). The Immunology of Epstein-Barr Virus Infection. The Royal Society, 356(1408), 475-488.
Odumade, O., Hogquist, K., & Balfour, H. (n.d.). Progress and Problems in Understanding and Managing Primary Epstein-Barr Virus Infections. Clinical Microbiology Reviews, 193-209.
Robertson, E. (2010). Epstein-Barr virus: Latency and transformation. Wymondham, Norfolk, UK: Caister Academic Press.
Taylor, G., Long, H., Brooks, J., Rickinson, A., & Hislop, A. (2015). The Immunology of Epstein-Barr Virus–Induced Disease. Annual Review of Immunology, 33.
