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The Epstein - Barr Virus
An introduction to one of the
world’s most common viruses
Presented by: Mary Shvarts
Shown here, Type 1 and Type 2 Downy cell, the common name for EBV infected lymphocytes.
General Information on EBV
Known as EBV, it is one of the best studied viruses.
Epstein- Barr may be the most common virus in the world,
affecting 80 - 90% of adults worldwide.
A latent, or lysogenic, virus - stops reproducing and remains
dormant for period of time before becoming active again.
During this latent period, the host has no detectable symptoms,
antibodies or virions.
Affects only humans
Targets B- lymphocytes
Linked to diseases such as infectious mononucleosis, Burkitt’s
lymphoma, nasopharyngeal carcinoma, and others.
Taxonomical Information
Linear, double stranded DNA virus; linear in mature virions,
circular in latent form
- ex/ lambda phage, adenoviruses
Family of Herpesvirudae – known as Herpes Type 6
Size - ~120 nm enveloped, 100- 110 nm capsid
- Subfamily Gammaherpesvirinae (lymphoprofilerative viruses)
- Genera Lymphocryptovirus
Icosahedral capsid symmetry, 162 capsomeres in arrangement
Capsid assembly at nuclear membrane
Nucleic acid replication in nucleus
Budding at nuclear membrane
How does EBV replicate?
EBV enters the cell by attaching to a host cell
surface receptor protein (C3d complement
protein).
Viral DNA forms into a circle in the host cell’s
cytoplasm, enters the cell’s nucleus, and
incorporates itself into the cell’s genetic
material.
Viral proteins are now expressed.
Ex/ EBNA- 1 – crucial to EBV’s survival
within the cell.
The host cell’s immune system recognizes
these proteins as foreign and releases T cells to
release cytokines in order to destroy the
infected host cell.
However, this process is not 100% effective
and the EBV virus continues infecting the host
for life in a few remaining B- cells in the host’s
blood and throat.
Image depicting viral attachment and
insertion of an EBV virion into a host
cell’s genome.
Infectious Mononucleosis
Also known as “glandular fever” and “mono,” this disease is most readily linked to
EBV.
Spread through contact with saliva, enters lymphatic tissues and infects B cells.
Infected B cells take on an atypical appearance and are known as Downy cells.
Symptoms include enlargement of lymph nodes and spleen, sore throat, headache,
nausea, mild fever, tiredness, and weakness.
Peak occurrence is with the 15-25 year old population. About 50% of college students
have no immunity to EBV. About 25-50% of these will contract the disease.
Lower economical classes acquire immunity through early childhood infection.
These infections usually have no symptoms and are undistinguishable from other mild
illnesses of childhood.
EBV does not cause problems during pregnancy.
No preventative measures should be taken.
No specific treatment is advised for infection except for treatment of symptoms,
which may include a course of steroids to control swelling of the throat and tonsils.
How to Determine Infection
Mono- Specific Testing
In most cases fever, pharyngitis
and swollen lymph glands are used
for a clinical diagnosis in
determining mono infection.
Serologic tests that show an
elevated white blood cell count,
increased total number of
lymphocytes, along with a positive
reaction to a “mono spot” test are
used as well.
If the symptoms of mono are
shown, a Paul- Bunnell heterophile
antibody test result is needed and
no further testing is necessary.
EBV- Specific Testing
IgM immunoglobins to the viral
capsid appear early in infection and
disappear within 4-6 weeks.
IgG’s appear in the acute phase,
peak 2-4 weeks after onset, decline
and remain for life.
Antibodies to the EBNA (EBV
nuclear antigen) can be seen by
immunoflourescent tests and are
only seen 2-4 months after onset.
False results are seen often and
pseudo-outbreaks have occurred
due to laboratory error.
Puerto Rico, 1999
Burkitt’s Lymphoma and other EBVlinked diseases
EBV does not cause disease, but its constant
gene translocations can. EBV antibodies are
produced in excess and if an oncogene
happens to be placed next to a gene for
antibody production, then oncogenes will
also be produced in excess. This results in
cancers, such as those seen below.
Rapid replication of EBV causes mistakes.
Nasopharyngeal carcinoma is a tumor of the nasal passages and throat that affects
up to 2% of people in southern China. It also occurs in parts of Southeast Asia,
northern Africa, and among those living in the Artic.
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Has been said to be a possible cause of Hodgkin’s disease.
Oral hairy leukoplakia involves a large amount of replication of EBV in cells
around the edge of the tongue, found mostly in AIDS sufferers.
Burkitt’s lymphoma is a non- Hodkins lymphoma which is commonly seen as a
malignant tumor of the jaw and abdomen, found mainly in children of central and
western Africa. Affects 8 in every 100,000 children in Africa and Papau New
Guinea..
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Link to presence of Malaria.
History of Epstein- Barr
In 1961 while working as a surgeon in
Uganda, Denis Burkitt reported a high
incidence of tumors in African
children, in certain geological areas.
This disease became known as Burkitt’s
lymphoma.
Due to the geographical coincidences,
researchers M.A. Epstein, Y.M. Barr,
and B.G. Achong began looking for
cancer- causing viruses from tumor
samples sent from Africa.
In 1964, with the help of an electron
microscope, they discovered a new
member of the herpes viruses now
known as the Epstein- Barr virus.
Uganda – where the Epstein- Barr virus first
was recognized in Burkitt’s lymphoma
New Progressions in the Fight Against
Epstein- Barr
Scientists at the Queensland Institute of Medical Research, located in Australia, are
working on a vaccine that utilizes a peptide identical to the EBV antigen EBNA-3 to
stimulate production of T cells.
This will serve as a vaccine against glandular fever and lymphoproliferative
diseases, not EBV.
A 2001 Harvard School of Public Health study shows that there may be a link between
EBV and Multiple scleroris.
Blood samples from 62,000 women were tested from 1989 to 1999. Elevated levels of
EBNA-2 antibodies were associated with a 4- fold increase in MS.
In a test done by doctors at the Nagasaki University Graduate School of Biomedical
Sciences, CD4 T cells obtained during the acute phase of mononucleosis were more
readily infected with HIV than were those taken during the convalescent phase. This
shows that EBV, like many STD’s, can facilitate HIV transmission and enhance HIV
replication.
Social class may have a role in EBV
infection with Hodgkin’s patients.
To the right – study results of EBV
infection vs the Townsend index.
References
Boggs MD, William. “Mononucleosis UPS Risk for HIV Infection.” MEDLINEplus. 25 Nov
2003. National Library of Medicine, National Institute of Health. 06 Dec 2003.
http://www.nlm.nih.gov/medlineplus/news/fullstory_14831.html
“Burkitt’s Lymphoma Resources.” Burkitts.org. 10 May 1999. 06 Dec 2003.
http://www.burkitts.org/
“Epstein-Barr Virus and Infectious Mononucleosis.” Centers for Disease Control and Prevention.
26 Oct 2002. National Center for Infectious Diseases. 03 Dec 2003.
http://www.cdc.gov/ncidod/diseases/ebv.htm
“High levels of Epstein- Barr Virus Antibodies in Women Linked to Risk of Multiple Sclerosis.”
Harvard School of Public Health. 26 Dec 2001. 06 Dec 2003.
http://www.hsph.harvard.edu/press/releases/press12262001.html
Hutchins, Andrew.“Epstein- Barr Virus.” UK Disease Directory. 28 Oct 2001. 04 Dec 2003.
http://www.diseasedir.org.uk/infect/vir02.htm
“Kissing the Epstein-Barr virus goodbye?” NOVA- Science in the News. Nov 1997. Australian
Academy of Sciences. 05 Dec 2003. http://www.science.org.au/nova/026/026key.htm
Prescott, Lansing M., John P. Harley, and Donald A. Klein. Microbiology, Fifth Edition. New
York: McGraw- Hill Higher Education, 2002.
“Uganda.” The World Factbook. CIA. 01 Jan 2003. 07 Dec 2003.
http://www.cia.gov/cia/publications/factbook/geos/ug.html