1. No category

NSF GK-12 Graduate Fellows Program
Award # DGE-0139171
University of North Carolina at Wilmington
Bubonic Plague
Reading Material to Accompany Activity
by
Elizabeth Buda
Department of Biological Sciences
Activity aligned with the 2001 North Carolina Standard Course of Study for 8th Grade Science: Goal # 2
Bubonic Plague: Yesterday's Scourge--and
Tomorrow's?
by Tina Blue
December 20, 2000
When you think of bubonic plague, no doubt you think of the Black
Death, the scourge of medieval Europe. What you probably don't realize
is that since the start of the twentieth century, North America has been
the world's largest reservoir of infection for bubonic plague and that
every year in this country people are infected with the plague and some
die of it.
What you also may not realize is that the antibiotics used to treat
plague are not as effective as they once were, and that eventually,
perhaps in the not too distant future, they will lose their efficacy
altogether. When that happens, we will see a worldwide pandemic that
will vastly overshadow the Black Death pandemic that depopulated
Europe during the Middle Ages.
The organism responsible for bubonic plague is Pasteurella pestis
(also called Yersinia pestis), which is spread by rodents and transmitted
to man by fleas parasitic on rodents.
The disease gets its name from one of its most characteristic signs,
a painful swelling of the lymph nodes in the groin area. The Greek word
for groin (boubon) is the root of the word "bubo," which is used to refer
to that swelling. A plague bubo can get as big as a large orange.
Lymph nodes in other parts of the body can also swell from the
infection, but the groin area is most often involved because it is easy for
an infected flea to reach and bite the legs, so the lymph nodes in the
groin provide the most convenient site for P.
pestis to set up shop.
The early signs of plague are easily mistaken for flu or other
illnesses: fever, chills, and weakness to the point of severe prostration.
Plague's ability to masquerade as flu in the early stages is particularly
unfortunate, since successful treatment depends on using the
appropriate antibiotics within a narrow time frame. Streptomycin,
aureomycin, and chloramphenicol are usually effective if administered in
the early stages of the disease. (Sometimes tetracycline is used in
addition to bolster the effect of one of those three antibiotics.)
Even in cases of pneumonic plague, which is far more virulent and
progresses even more rapidly than bubonic plague, if proper treatment
is begun within twenty-four hours of onset, a cure is possible. Where
pneumonic plague, the most virulent form of the disease, is concerned,
if treatment is begun after that twenty-four hour window has closed, the
antibiotics will do no good.
An early diagnosis of plague is essential for another reason.
Penicillin is useless against P. pestis, and if the physician mistakes
plague symptoms for those of another disease, precious time may be
lost while the wrong antibiotics are administered and given time to take
effect. (Although penicillin is not effective against P. pestis, it is
sometimes used in plague cases to treat secondary infections.)
Before the more effective drugs were developed, sulfadiazine was
used with some success to treat plague, and even now it is used if the
appropriate antibiotics are not available or if they are in short supply.
Sulfadiazine is frequently combined with the antibiotics, to enhance their
effectiveness, but most often it is used as a form of chemoprophylactic
(preventive) protection for those who have come in contact with plague
victims but who as yet show no sign of infection.
The Pasteurella pestis organism causes hemorrhages, which are
called plague spots when they appear on the skin. The dark color of the
spots and the extremely high mortality rate of the disease combined to
give bubonic plague its popular name during the Middle Ages, the Black
Death.
Bubonic plague is not directly communicable from one human to
another; it must be transmitted by the bite of an infected flea. But the
pneumonic form of the disease, which develops as a particularly virulent
form of pneumonia, can be directly transmitted. In pneumonic plague,
the bacilli are discharged into the atmosphere during coughing or
sneezing, or even during labored breathing. This form of the disease is
highly contagious, and the mortality rate for untreated pneumonic
plague is virtually 100%. Even when treatment is administered quickly,
recovery is by no means guaranteed.
RESERVOIRS OF INFECTION:
Plague persists as a chronic disease among approximately two
hundred species of rodents around the world. In this form, referred to as
"sylvatic plague," it is widely distributed in western North America,
southern South America, southern Africa, the Middle East, and central
Asia. These sylvatic plague reservoirs provide the infected fleas that
under optimal conditions (optimal for the disease organism, not for its
victims) will infect rats and man. The infection is passed from wild
rodents to "domestic" rodents--those inhabiting large cities in close
association with man.
Until the first years of the twentieth century, plague was unknown in
North and South America. That is ironic, since those two continents now
constitue the world's largest loci of infection. The infection of the "New
World" occurred as a consequence of the third great plague pandemic,
which officially began in 1894, though many experts cite 1850 as its real
starting point.
The first pandemic occurred during the sixth century a.d., during the
reign of the Emperor Justinian. The second pandemic occurred during
the Middle Ages--it is the one we call the Black Death. The third
pandemic lasted until 1959. Many of you who are reading this article
don't realize it, but you are a survivor of the third great bubonic plague
pandemic, which killed far more people--over thirteen million!--than the
other two pandemics combined.
In 1894 a few cases of plague were documented in Canton, and from
there it spread to Hong Kong. Although the initial outbreak was relatively
small, the disease was quickly carried to many parts of the world by
ocean-going vessels. In its westward course, the plague reached India,
and then Africa and Europe (especially Spain, Portugal, Italy, and Great
Britain). It also spread eastward to the Philippines, Australia, Japan,
Hawaii, and the Pacific coasts of North and South America.
PLAGUE IN THE UNITED STATES
Human plague was diagnosed for the first time in the United States
in 1900, at San Francisco, and shown to be present among rats in that
city in 1902. At first business interests, in collusion with conservative
politicians in both the city and the state, resisted official
acknowledgment of plague as well as all official efforts to control its
spread. This refusal to address the problem for fear of hurting business
led to a far worse outbreak than would otherwise have occurred.
Eventually, other states quarantined California, and forced them to deal
with the plague after all.
Many of the deaths during the third pandemic were concentrated in
the less developed parts of the world, especially in India between 1898
and 1928. There were several hundred plague deaths in the United
States during the last century, including several in the 1990s.
At present the plague is largely controlled throughout the world, but it
remains endemic in some rural areas of Asia, South Africa, and South
America. Sometimes, as in Vietnam during the 1960s, as a result of war
conditions, it flares up into epidemic proportions.
PROBLEMS IN PREVENTION AND CONTROL
One reason why we need to maintain a healthy respect for the
possibility of another great plague pandemic is that although the
reservoirs of infection are rural, human commerce, urban living
conditions, population density, and encroachment on and development
of wilderness areas significantly influence the conditions that lead to the
spread of plague.
The introduction of DDT during World War II was a major step in
getting control of
P. pestis. The U.S. military used DDT to suppress fleas in 1944 at
Dakar, Senegal. There was also a directed effort to educate the
inhabitants of the region in sanitation methods and rat control.
Other preventive measures against plague include ratproofing
buildings and reducing living and breeding sites for rats, especially
docks and warehouses. Ships are also ratproofed and periodically
fumigated, and vessels and cargoes from plague areas are inspected
for rats. Periodic surveys are taken in endemic and potentially epidemic
areas to assess the prevalence of rats and fleas, and rat populations in
urban areas are suppressed by means of poisoning and trapping.
When a plague outbreak occurs, the governments of the nations
involved are required by international law to notify the World Health
Organization (WHO) as well as the governments of adjacent countries.
Despite such precautions, however, the ease and speed of global
travel have created a situation where any communicable disease is
likely to escape its place of origin. Furthermore, many agencies--both
national and international--responsible for monitoring and controlling
potential plague outbreaks are chronically underfunded and
understaffed, since most of the world's governments have grown
complacent about the risk of a fourth plague pandemic.
Their complacency is far from warranted. In the first place,
rodenticides and insecticides used to control rat and flea populations in
urban areas are no longer as effective as they once were. In several
U.S. cities, between one-fourth and one-half of all rats and mice are
now resistant to warfarin and to other chemical agents used to control
them. DDT is no longer as effective in flea control, and, besides, it is
widely banned in the advanced nations.
In the second place, it may not be long before antibiotics used to
treat plague become completely useless against the disease. In 1998,
the first case of human plague that showed total resistance to all known
antibiotics was reported. Even one such strain of resistant P. pestis
could spell catastrophe. Once a bacterium develops resistance to a
drug, that resistance soon spreads to all such bacteria by a process
called "infectious drug resistance." Some bacteria carry an "R" (for
"resistance") factor, and can pass their resistance along, not only to the
same bacteria, but even to other bacteria altogether.
Escherichia coli, the common colon bacillus, is frequently resistant to
one or more antimicrobial drugs. Some strains of E. coli are resistant to
all known antimicrobials. And E. coli often carry R factors. So a common
bacterium found in the human body and in river water all over the world
can pass antimicrobial resistance to a wide variety of disease-causing
organisms--including P. pestis.
If an outbreak of multiply resistant plague occurs anywhere in the
world, the chances are high that it will spread globally. Should that
occur, our innumerable large urban centers are at great risk for
epidemic plague, not only because crowded urban conditions are ideal
for establishing a plague epidemic, but also because so many rodents
and fleas have developed resistance to the rodenticides and
insecticides we would normally use to control their populations.
The fourth great bubonic plague pandemic could occur at almost any
time. If and when it does, its effects will be far more devastating than
those of the Black Death.
(from--http://www.salvoblue.homestead.com/plague.html)
Bubonic Plague-AIDS Connection
By Michael Davis
Theories that some
people have a
natural immunity
to HIV are nothing
new. About five
years ago, research
first began to
indicate that
certain genetic
HIV attempting to bombard a white blood cell.
PHOTO COURTESY OF
mutations might
provide protection THIRTEEN/WNET NEW YORK
against AIDS.
What is new, however, is that research supporting these theories slowly has been
mounting and has begun to grab the attention of the mainstream American population.
Case in point: On October 30, PBS will air "Mystery of the Black Death," the first of five
new episodes from Thirteen/WNET New York's Secrets of the Dead series.
Interestingly, the title gives no indication that AIDS or HIV immunity also will be
explored. So, when that issue finally is introduced (about three-quarters of the way into
the program), some viewers are likely to be in for a pleasant little intellectual shock.
The documentary explores a possible link between 14th-Century survivors of the bubonic
plague (or the Black Death, as it also is known) and modern-day people who engage in
high-risk sexual behavior, but appear to be immune to HIV infection. That link, the film
asserts, is the presence of an abnormal version of the CCR5 gene known as CCR5-delta
32.
To support this startling claim, "Mystery of the Black Death," part of a series well known
for using modern technology to reexamine old events, looks at the work of two different
research scientists.
Geneticist Steven O'Brien, of the National Institutes of Health in Washington, D.C., leads
an international team of researchers who identify two groups of individuals that survived
close contact with the plague in England around the year 1670. One group included
people who became ill from the devastating bacterium and recovered. The other was
composed of persons who never became ill from it.
In an effort to discover why the survivors were able to recover, O'Brien and his team
tested the descendants of those survivors and found that the delta-32 mutation was
present in a significant percentage of them. Further studies led to speculation that
survivors with one copy of the mutation (inherited from a single parent) were able to
recover, while persons lucky enough to have had two copies (one inherited from each
parent) never got sick.
The other researcher, Bill Paxton, of the Aaron Diamond Center for AIDS Research in
New York, focused his study on Steve Crohn, a gay male who came of age in California
during the 1970s. Crohn has lost more than 80 friends and lovers to AIDS, yet he
repeatedly has tested HIV-negative.
Paxton took a sample of Crohn's
immune cells, bombarded them with
3,000 times the amount of virus that
typically causes infection, and found the
virus still was unable to penetrate his
immune cells. Additional testing
revealed that Crohn possesses two
copies of the delta-32 mutation.
Though the documentary fails to
Steve Crohn, a gay man whose genetic
establish that Crohn is a definite
resistance
to HIV may lead to treatments and a
descendant of plague survivors, it seems
cure for AIDS.
to rely on basic reasoning: The genes of
PHOTO COURTESY OF
THIRTEEN/WNET NEW YORK
survivors are passed down to future
generations. The bubonic plague
"weeded out" Europeans without the mutated gene. People with European ancestors
would be more likely to have this gene, and vice versa. And Crohn happens to be white
and of European descent.
Apparently, the normal CCR5 gene puts receptors on immune cells that act like doors
allowing HIV to enter and hijack a cell. Without that door, the virus can't get in. When
the gene is abnormal, no door exists.
"Mystery of the Black Death" is a thoughtful and well-organized production. It does a
great job of presenting scientific research in layman's terms. Although the "special
effects" aren't particularly special (and probably could have been done without), a good
narrative pretty much makes up for this drawback.
Arguably, one of the best features of the work is its brief look into the psyche of a gay
man who, after a yearlong battery of tests, is told that his blood seems incapable of
contracting HIV. However, most researchers stop short of claiming that people like
Crohn are completely immune to HIV.
"I know there's this whole kind of survivor's guilt, but I can't relate to it," Crohn said in a
recent interview. "I do still feel a tremendous loss that's changed my life. There's no
trade-off for losing 80 of your friends, or seeing families, your best friend's parents,
devastated by the loss of their son, who died within 30 days."
Crohn, who actively sought out studies in which to participate, feels that he has made a
contribution. He hopes the research of which he has been a part can result in a drug that
will help others.
How likely, in fact, is it that this research eventually will lead to a cure for AIDS? Could
the same genetic mutation ward off infection by both the plague bacteria and HIV?
"Mystery of the Black Death" probes these questions and many others. This documentary
dramatizes a harsh way of life during one of the world's most devastating epidemics in
earlier times and follows modern scientists on their quest for answers that may change the
future of AIDS treatment.
(from--http://www.lavendermagazine.com/193/193_go_38.html)
Could the Black Death protect against
HIV?
People who survived the Black Death could have passed on a mutation that
prevents the human immunodeficiency virus entering cells. | By David
Nicholson
LONDON Several teams of scientists around the world have, for some time, been
studying the possibility that a genetic mutation perpetuated by the organism responsible
for bubonic plague, or the Black Death, in the Middle Ages - Yersinia pestis - might give
people now carrying the mutation increased resistance to the Human Immunodeficiency
Virus (HIV) compared to non-carriers. New research has thrown doubt on the microorganism that was thought to have caused the Black Death, but the link to HIV resistance
seems to remain.
Sue Scott and Chris Duncan from the University of Liverpool have suggested that the
bacterium Y. pestis — held to be the causative organism for bubonic plague since the
19th century — may not have been responsible for the epidemic after all. In their book,
'Biology of Plagues' (Cambridge University Press, 2001) they proposed that the culprit
was most likely a filovirus, similar to the Ebola virus. This theory is based on evidence
that emerged after sifting through old parish records of the many towns affected by the
plague and then tracking how the disease spread throughout Britain and Europe.
So how does this link to increased resistance to HIV? In a study published in the
American Journal of Human Genetics (Am J Hum Genet 1998, 62:1507-1515) Stephen
O'Brien and colleagues at the US National Cancer Institute, used coalescence theory to
interpret modern haplotype genealogy. They found that a genetic mutation that gives its
carriers protection against the HIV virus became relatively common among white
Europeans about 700 years ago — the same period that the Black Death swept into
Europe. The team also concluded that the geographic cline of the mutation frequencies
and its recent emergence were consistent with a strongly selective historic event (such as
an epidemic of a pathogen), driving its frequency upwards in populations whose
ancestors survived the Black Death.
The mutation occurs on the gene for CCR-5, a receptor on the surface of macrophages.
When a person becomes infected with HIV, the virus latches onto CCR5 and another
protein — CD-4 — to be transported inside the macrophages.
CCR-5 is disabled in people with the full mutation, and so HIV is unable to gain access to
the macrophages. If an individual inherits the mutant gene from both parents, they are
essentially immune to HIV infection. People with one mutant and one normal gene can
be infected, but tend to survive longer than infected people with two normal CCR-5
genes. It seems as though people without the mutation, called CCR5-_32, were killed by
the Black Death, so that those with the mutation survived to reproduce and increase its
prevalence today.
In 2000, another team of scientists, from Copenhagen's Hvidovre Hospital, investigated
why many Europeans appeared to be resistant to HIV. Jesper Eugen-Olsen teamed up
with archaeologist and carbon-dating specialist Kaare Lund Rasmussen from the Danish
National Museum and analyzed genetic material from ancient bone tissue to try to solve
the mystery.
"It always puzzled scientists in the field that the mutation never occurs in Asian or
African populations, but only among European Caucasians," said Eugen-Olsen. It is
much more prevalent in the North and tapers off towards the Mediterranean, meaning that
only eight out of 100 Southern Italians carry the mutation, compared to one in four
Danes.
The Danish group rejected the idea that the mutation became more prevalent as a result of
the Black Death because the epidemic began in Sicily (in the South) and spread north to
Scandinavia. This direction of travel would have predicted that the prevalence of the
mutation would have become higher in the South than in the North, which is the reverse
of what actually happened.
Assuming that the mutation arose in Scandinavia, Eugen-Olsen's team concentrated on
determining the time of the major spread of the mutation by examining bones found in
Denmark, dating from the last Ice Age, around 8000 BC to 1950 BC. In particular, they
focused on the time between 1800 and 2600 BC, a Mesolithic period of massive change
and migration.
Their findings suggested that the CCR-5-_32 mutation was already highly prevalent in
Denmark before the Black Death. Rasmussen reported: "There is support in the fact that
the distribution of the Single Grave Culture in Northern and Middle Europe matches that
of the high prevalence of 32_." This meant that an epidemic decimating the Stone Age
population could explain the archaeological observations as well as the distribution of the
32_ mutation.
They proposed that people with the genetic mutation were then more likely to survive the
Black Death, passing on the mutation to current generations and conferring resistance to
HIV.
Although the potential cause of the Black Death might have changed, researchers in the
field still suspect that exposure to it may have passed on resistance to HIV. Since the
CCR5 mutation provides protection against the entry of a virus, there's good reason to
believe that what caused the Black Death was also viral, and targeted the same cells as
HIV," concluded Scott.
(from-- http://www.biomedcentral.com/news/20010713/04/)
Drug-resistant bubonic
plague found in 16-year old
boy
By: Tamar Simon, September 9, 1997
Researchers from France and
Madagascar have reported the firstever discovery of an antibiotic-resistant strain of bubonic plague.
The strain, identified as Y. pestis 17/95, was found in a 16-year
old Madagascar boy in 1995. It proved resistant to eight different
drugs, including streptomycin, tetracycline and spectinomycin,
which are commonly used to treat the disease. The boy was also
treated with an antimicrobial drug containing sulpha, which
appeared to have saved him.
The researchers reported their findings in Thursday's issue of the
New England Journal of Medicine. The article noted that the fact
that the bacteria could acquire drug resistance once indicated
"that such a clinically ominous event may occur again." And in an
editorial to the article, Dr. David T. Dennis and Dr. James K.
Hughes of the Centre for Disease Control and Prevention in
Atlanta, called the results "another grim reminder that emerging
infectious diseases and antimicrobial resistance in one location
can pose serious problems for the entire world."
Bubonic plague, also known as the "black death", wiped out most
of Europe's population in the 14th century in less than 20 years,
and never entirely disappeared. It is caused by a highly virulent
organism spread by the bite of fleas found on rats or wild
rodents such as squirrels and prairie dogs. Person-to person
spread of the disease is rare, but can occur when there is an
outbreak.
Symptoms include the sudden onset of chills, fever and rapid
weakness. It is fatal if not treated promptly with the right
antibiotic. In the United States, there have been 375 reported
cases of the plague since 1950, with a fatality rate of 15 per
cent.
Dr. Dennis speculates that if resistance was transferred to the
plague bacteria from other organisms, it probably occurred in the
body of a rat, "the normal host for the plague in Madagascar."
The rat could have ingested the other antibiotic-resistant
organisms by chewing on the bones of livestock fed antibiotics, a
practice that gives organism in such livestock resistance.
While Dr. Dennis says it is impossible to know whether the
Madagascar discovery is an isolated finding, or whether there will
be more cases of resistant plague, he says it serves as a
"warning to take steps to stop the spread of the disease."
(from-- http://exn.ca/Stories/1997/09/04/02.asp)
Far from the deadliest epidemic.
The Bubonic Plague.
Just mention the name and you will send shivers down the spine of many people.
There is no doubt that this disease was deadly. Deadly and gruesome to watch.
The death rate was 90% for those exposed to the bacterium. It was transmitted by the
fleas from infected Old English black rats. The symptoms were clear: swollen lymph
nodes (buboes, hence the name), high fever, and delirium. In the worst case, the lungs
became infected and the pneumonic form was spread from person to person by coughing,
sneezing, or simply talking.
From the time of infection to death was less than one week.
There were three major epidemics - in the 6th, 14th, and 17th centuries.
The death toll was 137 million victims.
As a result, the plague is considered to be the worst epidemic of all time, but it wasn't
(not that we are downplaying the severity of the plague).
At its worst, the bubonic plague killed 2 million victims a year.
This is certainly a bad situation, but there is one that is worse.
The pandemic (an epidemic that is spread worldwide) that killed at least 25 million
people in one year.
A disease that is largely forgotten.
A disease that occurred in the 20th century!
I know what you're thinking - AID's, Syphilis, or the dreaded Ebola.
All are wrong.
It was the influenza of 1918-1919, right after World War I (the war killed 9 million men
in 4 years)
This was no minor disease - everyone on the planet was at risk.
And it was started right here in the good old U. S. of A.
In one year, nearly twenty million cases were reported in the United States, accounting
for almost one million deaths.
The cause is still unknown, but is believed to have been a mutated swine virus.
It all started on the morning of March 11, 1918 at Camp Funston, Kansas.
A company cook named Albert Mitchell reported to the infirmary with typical flu-like
symptoms - a low-grade fever, mild sore throat, slight headache, and muscle aches. Bed
rest was recommended.
By noon, 107 soldiers were sick.
Within two days, 522 people were sick. Many were gravely ill with severe pneumonia.
Then reports started coming in from other military bases around the country.
Thousands of sailors docked off the East Coast were sick.
Within a week, the influenza was hitting isolated places, such as the island of Alcatraz.
Whatever the cause, it was clearly airborne.
Within seven days, every state in the Union had been infected.
Then it spread across the Atlantic.
By April, French troops and civilians were infected.
By mid-April, the disease had spread to China and Japan.
By May, the virus was spread throughout Africa and South America.
The actual killer was the pneumonia that accompanied the infection.
In Philadelphia, 158 out of every 1000 people died. 148 out of 1000 in Baltimore. 109 out
of 1000 in Washington, D. C..
The good news (if there was any) was that the disease peaked within two to three weeks
after showing up in a given city. It left as quickly as it arrived.
The United States death toll was a total of 850,000 people, making it an area of the world
that was least devastated by this virus.
Sixty percent of the Eskimo population was wiped out in Nome, Alaska.
80-90% of the Samoan population was infected, many of the survivors dying from
starvation (they lacked the energy to feed themselves).
Luxury ocean liners from Europe would arrive in New York with 7% less passengers
than they embarked with. The confined area of the ship was especially conducive to the
spread of the disease.
In the end, 25 million people had died. Some estimates put the number as high as 37
million.
Eighteen months after the disease appeared, the flu bug vanished and has never shown up
again.
So what happened?
Until recently, no one was really sure. In March of 1997, the news broke that researchers
at the Armed Forces Institute of Pathology in Washington, D. C. had isolated genetic
material from the virus.
This was no easy task. The living virus is no longer around. It turns out that while
conducting autopsies in 1918, Army doctors had preserved some specimens in
formaldehyde. One of these jars contained the lungs of a 21 year old soldier that died on
September 26, 1918.
Bingo!
The researchers spent nearly two years extracting just seven percent of the genetic code,
but the evidence gathered has provided a great wealth of information.
It appears that the virus passed from birds to pigs and then to humans. These are the
deadliest of all viruses. The viruses tend to remain stable in the birds, but occasionally
they infect pigs. Of course, the pig immune system kicks into action and the virus is
forced to mutate to survive. Both the Asian flu (1957) and the Hong Kong flu (1968),
which were not as deadly, mutated from pig viruses.
The scary part is that it could happen again - and we're not prepared for it.
(From-- http://home.nycap.rr.com/useless/bubonic_plague/)
ISAT 351
Immunology Project
Genetic Resistance to AIDS
Kai Degner
Ryan Vinton
Curtis Jones
Carl Randecker
(http://www.avert.org/virus2.htm)
Short Overview
AIDS is an immunodeficiency disease that has been in the forefront of the public eye for
the past two decades. As of December 2001, 40 million people worldwide were infected
with either HIV or AIDS. Much time and effort is being devoted to finding cures for this
lethal disease. Researchers take steps towards a solution everyday, but no one has come
up with a way to completely prevent the HIV virus from causing AIDS or curing a patient
from AIDS. One issue that particularly intrigues researchers today is the fact that some
people seem to naturally be able to prevent the HIV virus from progressing to AIDS.
AIDS attacks the patients T-cells because it has sites on which the virus can bind. Most
human T-cells are equipped with two specific binding sites that are crucial in contracting
an HIV infection. These two proteins – CD4 and CCR5 – can be present on the T-cell
surface. However, it has been found that the GP-120 protein on HIV first binds loosely
to the CD4 protein, and then secures itself to the T-cell by binding to the CCR5 site.
Without the second bidning to the CCR5, the virus does not bind closely enough to infect
the T-cell. Recent discoveries show that some humans have a mutation in their CCR5
protein. The mutation distorts the structure of the CCR5 protein such that the HIV virus
cannot not bind closely enough to infect the T-cell. Without the spread of infection to Tcells, the HIV attack is thwarted.
The Link between The Bubonic Plague
and HIV Resistance
Recent research has found convincing evidence that the resistance to HIV stems from
inherited genes passed down by survivors of the bubonic plague in Europe. People who
contain a mutated CCR5 gene are resistant to HIV infection. The resistance to HIV
varies according to the number of mutated CCR5 genes inherited. A person obtaining
two mutated CCR5 genes will be immune to the HIV virus. However, someone
containing one mutated CCR5 gene will be resistant to HIV but not necessarily immune.
If a person with one mutated CCR5 gene becomes infected the infection tends to have a
more lethargic course of infection, than someone without a mutated CCR5 gene.
Researchers believe that these mutations are inherited from survivors of the bubonic
plague in Europe. These researchers found that these mutations are more common in
Swedes, and become less common as one moves south and east from Northern Europe. It
is believed that this gene has been present for approximately 700 years, which would date
to the era of the bubonic plague in Europe(circa 1350). The plague is a bacterial
infection that attacks macrophages, similar to the HIV virus. It is unknown whether or
not the CCR5 receptor was used as the “loading dock” for the infection. This leads room
to believe that other viruses could be responsible for this gene mutation such as syphilus,
small pox, Mycobacterium tuberculosis, or Salmonilla.
HIV Resistance Questions
Why does a defective gene for CCR5 make the HIV virus unable to spread in the blood?
-This is because the virus can not bind to the CCR5 and infect the T-cell.
What immune system receptor gene does the HIV virus use as a “loading dock”, and how
is this receptor involved in resistance to the AIDS virus?
-
The immune system receptor gene that the HIV virus uses as a “loading dock”
is the CCR5 Receptor. The CCR5 receptor is involved in the resistance to
AIDS because in some cases, there is a mutation in this receptor resulting in
the inability of the HIV virus to use it as a “loading dock”. People who have
inherited the mutated gene from both parents are resistant to the HIV virus.
Bibliography
O’Brien, Steven, J. & Micheal Dean. In Search of AIDS_Resistance Genes. Scientific
American. September, 1997. Online in Internet. URL:
http://seattletimes.nwsource.com/news/nation-world/html98/plag_051098.html
http:/www.ucl.ac.uk/biology/Goldstein/public/stephens
(from-http://www.isat.jmu.edu/users/klevicca/case_studies/351%20aids%20resistance.doc)
The Bubonic Plague
Almost half of the people of Western Europe died in a
great sickness known as the Bubonic Plague. The plague was also referred
to as "the Black Death" because the skin of diseased people turned a dark
gray color. It apparently began in China's Gobi Desert, and it killed about
35 million Asian people. When sailors traveled to Asia, rats returned with
them to Europe. Fleas living on the blood of infected rats then transferred
the disease to the European people.
In 1347, Italian merchant ships returned from the Black Sea, one of the
links along the trade route between Europe and China. Many of the sailors
were already dying of the plague, and within days the disease had spread
from the port cities to the surrounding countryside. The disease spread as
far as England within a year.
The Europeans were susceptible to disease because they lived in crowded
surroundings with very poor sanitary conditions. The Europeans often ate
stale or diseased meat because refrigeration had not yet been invented.
Also, medicine was primitive and unable to remedy an illness that modern
technology might have cured. Bad medical advice also advanced the
plague. People were often advised to not bathe because open skin pores
might let in the disease.
Death from the plague was horrible, but swift. The Italian writer
Boccaccio said victims often "ate lunch with their friends, and ate dinner
with their ancestors in paradise." The first signs were generally aching
limbs, and vomiting of blood. Then the lymph nodes would begin to swell.
The lymph nodes are glands found in the neck, armpits, and groin. The
swelling continued for three or four days until the lymph nodes burst. The
swiftness of the disease, the enormous pain, the grotesque appearance of
the victims, all served to make the plague especially horrifying.
Some Europeans believed the plague was a sign from God. Groups
known as flagellants tried to atone for the sins of the world by inflicting
punishments upon themselves. They also had a tendency to persecute Jews
and even clergymen who spoke out against them. Pope Clement VI
condemned the flagellants, but they continued to reappear in times of
plague. The Bubonic Plague continued to affect cities from time to time
for hundreds of years. It still exists and is common among rodents. We
have a cure for the disease, but occasionally people in isolated places still
die from the Bubonic Plague.
(from-- http://www.mrdowling.com/703-plague.html)