Microbiology and Immunology

Hepadnaviruses WORLD OF MICROBIOLOGY AND IMMUNOLOGY

264

•

The speed at which hemorrhagic fevers appear and end

in human populations, combined with their frequent occur-

rence in relatively isolated areas of the globe has made

detailed study difficult. Even though some of the diseases,

such as Argentine hemorrhagic fever, have been known for

almost 50 years, knowledge of the molecular basis of the dis-

ease is lacking. For example, while it is apparent that some

hemorrhagic viruses can be transmitted through the air as

aerosols, the pathway of infection once the microorganism has

been inhaled is still largely unknown.

The transmission of hemorrhagic viruses from the ani-

mal reservoir to humans makes the viruses the quintessential

zoonotic disease. For some of the viruses the host has been

determined. Hosts include the cotton rat, deer mouse, house

mouse, arthropod ticks, and mosquitoes. However, for other

viruses, such as the Ebola and Marburg viruses, the natural

host still remains undetermined. Outbreaks with the Ebola and

Marburg viruses have involved transfer of the virus to human

via primates. But, whether the primate is the natural host, or

acquired the virus as the result of contact with the true natural

host is not clear.

Another fairly common feature of hemorrhagic diseases

is that once humans are infected with the agent of the disease,

human-to-human transmission can occur. Often this transmis-

sion can be via body fluids that accidently contact a person

who is offering care to the afflicted person.

Hemorrhagic diseases typically begin with a fever, a

feeling of tiredness, aching of muscles. These symptoms may

not progress further, and recovery may occur within a short

time. However, damage that is more serious can occur, which

is characterized by copious bleeding, often from orifices such

as the mouth, eyes, and ears. More seriously, internal bleeding

also occurs, as organs are attacked by the infection. Death can

result, usually not from loss of blood, but from nervous system

failure, coma, or seizures.

Hemorrhagic diseases are difficult to treat. Vaccines are

available to only yellow fever and Argentine hemorrhagic

fever. For the remaining diseases, the best policy is to curb the

potential for human interaction with the natural reservoir of

the microbe. For example, in the case of hantavirus pulmonary

syndrome, control of the rodent population, especially after a

rainy season when numbers naturally increase, is a wise

course. Insect vectors are controlled by a concerted campaign

of spraying and observance of precautionary measures (e.g.,

use of insect repellent, proper clothing, insect netting over

sleeping areas, etc.).

See alsoPublic health, current issues; Viruses and response to

viral infection

HHepadnavirusesEPADNAVIRUSES

Hepadnaviridae is a family of hepadnaviruses comprised by

two genera, Avihepadnavirus and the Orthohepadnavirus.

Hepadnaviruses have partially double strands DNA(partial

dsDNA virion) and they replicate their genome in the host

cells using reverse transcriptase and are therefore, termed

retroviruses. Their virion DNA, invades the hepatocytes (i.e.,

liver cells) of vertebrates, which are their natural hosts. When

hepadna retroviruses invade a cell, a complete viral dsDNA is

made before its random integration in one of the host’s chro-

mosomes, and is then transcribed into an intermediate mes-

senger RNA(mRNA) into the hosts’nucleus. The viral mRNA

then leaves the nucleus and undergoes reverse transcriptase,

mediated by a viral reverse transcriptase enzyme that tran-

scribes complementary strands of complementary dsDNA in

the cell cytosol, thus forming new partial dsDNA virions.

Orthohepadnavirusis the pathogenic agent that causes

chronic hepatitis(Hepatitis type B) in mammals, which may

eventually lead to either cirrhosis or liver cancer if not detected

and treated. Hepatitis B Virus or HBV, the prototype member of

the family Hepadnaviridae, is transmitted by both infected

blood (blood transfusions, grafts) and body fluids (usually

through sexual relations with infected partners). HBV com-

prises several viral species that also infect the liver cells of

orangutans, dogs, and other mammalians besides man. Vaccines

for both human Hepatitis B and several forms of animal

Hepatitis B (lions, cats, dogs) are available as a form of disease

prevention. All Hepadnaviridae viruseshave a high affinity

with liver cells (hepatotropy) and the viruses of the genus

Avihepadnavirus,also known as avian hepadnaviruses, have as

targets the liver of birds, such as storks, ducks, herons, etc.

See also Animal models of infections; Antiviral drugs;

Hepatitis, hepatitis viruses and tests; Interferons; Virology

HHepatitis and hepatitis virusesEPATITIS AND HEPATITIS VIRUSES

Hepatitis is inflammationof the liver, a potentially life-threat-

ening disease most frequently caused by viral infections but

which may also result from liver damage caused by toxic sub-

stances such as alcohol and certain drugs. Hepatitis viruses

identified to date occur in six major types: hepatitis A HAV),

hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and

hepatitis E (HEV) and hepatitis G (HGV). All types are poten-

tially serious and, because clinical symptoms are similar, pos-

itive identification of the infecting strain is possible only

through serologic testing (analyzing the clear, fluid portion of

the blood). Symptoms may include a generalized feeling of

listlessness and fatigue, perhaps including mental depression,

nausea, vomiting, lack of appetite, dark urine and pale feces,

jaundice (yellowing of the skin), pain in the upper right por-

tion of the abdomen (where the liver is located), and enlarge-

ment of both the liver and the spleen. Severe cases of some

types of hepatitis can lead to scarring and fibrosis of the liver

(cirrhosis), and even to cancer of the liver.

Epidemicsof liver disease were recorded as long ago as

Hippocrates’ time and, despite major advances in diagnosis

and prevention methods over the past two decades, viral hep-

atitis remains one of the most serious global health problems

facing humans today.

The incidence and spread of HAV is directly related to

poor personal and social hygieneand is a serious problem not

only in developing countries where sanitation and water

womi_H 5/6/03 3:20 PM Page 264