Chapter 38: Human Diseases Caused by Viruses

BIOL 3702 Lecture Outline
Chapter 38: Human Diseases Caused by Viruses

Airborne Diseases
Chickenpox (varicella) and shingles (zoster)

Caused by varicella-zoster virus, a member of Herpesviridae Acquired by inhaling virus-laden droplets into the respiratory system Incubation period is 10 to 23 days after which small vesicles appear on face and
upper trunk
Can be prevented or infection shortened with attenuated vaccine or the drug
acyclovir
Infection confers permanent immunity from chickenpox, but does not rid individual
of virus
Virus
enters a latent stage in the nuclei of sensory nerve roots can reactivation of virus leads to shingles
Stress
Influenza (flu)
Caused by orthomyxoviruses that can undergo frequent antigenic variation
Antigenic Antigenic
drift-small variation shift-large variation
Animal reservoirs are important (e.g., chickens and pigs) and contribute to
antigenic shifts
Virus is acquired by inhalation or ingestion of virus-contaminated respiratory
secretions
Influenza is characterized by chills, fever, headache, malaise, and general
muscular aches and pains

Diagnosis can be confirmed by rapid serological tests Death can result from pneumonia caused by secondary bacterial infection Treatment is focused on alleviating symptoms, but some antiviral drugs have been
shown to decrease duration and symptoms of type A influenza
Measles (rubeola)
A skin disease with respiratory spread caused by Morbillivirus, a member of family
Paramyxoviridae
After 10-21 day incubation, cold-like symptoms develop, followed by a rash Sometimes a diagnostic oral lesion, a Koplik spot, is formed On rare occasions can develop into subacute sclerosing panencephalitis MMR (measles, mumps, and rubella) vaccine is used for prevention
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Copyright 2004 by Chester R. Cooper, Jr.

Morbidity and mortality
United
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States - 2,000 - 3,000 cases per year mostly in unvaccinated individuals
Less-developed
countries - measles among children is extremely high: 50 million infected, 4 million die
Mumps
Caused by mumps virus, a member of the genus Rubulavirus in the family
Paramyxoviridae
Spread in saliva and respiratory droplets; portal of entry is the respiratory tract Causes swelling of salivary glands Meningitis and inflammation of testes are complications, especially in post-
pubescent male
Therapy is supportive and the MMR vaccine is used for prevention
Respiratory syndromes and viral pneumonia

Acute respiratory syndromes
Caused
by a variety of viruses collectively referred to as acute respiratory with rhinitis, tonsillitis, laryngitis, and bronchitis
viruses
Associated Immunity
resulting from infection is incomplete and re-infection is common
Viral pneumonia is clinically nonspecific, and symptoms may be mild or severe
(death is possible)
Respiratory syncytial virus (RSV) is the most dangerous cause of respiratory
infection in young children

RSV
is a member of the RNA virus family Paramyxoviridae cells form syncytia (multinucleated large cells) U.S. cases per year with 4,000 deaths
Infected 90,000
Rubella (German measles)

Caused by rubella virus, a ssRNA virus of family Togoviridae Virus is spread by respiratory droplets Resulting infection is mild in children (a rash) Disastrous for pregnant women in first trimester causing congenital rubella
syndrome
Premature Congenital Fetal
delivery defects
death
No treatment is indicated
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A vaccine (MMR) is available
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Smallpox (variola)
Caused by variola virus, a dsDNA virus belonging to the family Poxviridae Virus is transmitted by aerosol or contact Symptoms include severe fever, prostration, rash, toxemia, and septic shock Death results from toxemia associated with immune complexes and hypotension Virus was eradicated as the result of a vigorous worldwide vaccination program Eradication was made possible for several reasons
Disease There It
has easily identifiable clinical features
are virtually no asymptomatic carriers
infects only humans (there are no animal or environmental reservoirs)
It has a short period of infectivity
Arthropod-Borne Diseases
General features of arthropod-borne diseases

Viruses multiply in tissues of insect vectors without producing disease, and vector
acquires a lifelong infection

Three clinical syndromes are common
Undifferentiated Encephalitis
fevers, with or without a rash
- often with a high fatality rate fevers - frequently severe and fatal
Hemorrhagic
Infection provides permanent immunity For many of the diseases

No
vaccines are available is usually supportive
Treatment
Colorado Tick Fever

Caused by Coltivirus (RNA virus) Tick-borne; main reservoirs are ground squirrels, rabbits, and deer Symptoms include abrupt onset of fever, chills, severe headaches, photophobia,
and muscle pain

Serology is used to confirm diagnosis No treatment except supportive therapy Prevention involves avoiding ticks
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West Nile Fever (encephalitis)

Caused by a flavivirus that primarily occurs in the Middle East, Africa, and
Southwest Africa
Appeared in the U.S. (New York) in 1999 and has spread to virtually every state
causing disease and death

Carried by infected mosquitoes that feed on infected birds (sparrows and crows) Infection produces viremia that leads to lymphadenopathy and rash Can cause fatal encephalitis in susceptible persons (young, old, AIDS patients,
diabetics, etc.)
Only 1 in 5 infected people show signs of infection with only 1 in 100 developing
serious disease
Treatment: mosquito control
Yellow Fever
Mosquito-borne Two patterns of transmission
Urban
cycle - human-to-human transmission cycle - monkey-to-monkey and monkey-to-human transmission
Sylvan
Early symptoms include fever, chills, headache, backache followed by nausea and
vomiting
Severe cases lead to jaundice, lesions and hemorrhaging Prevention and control is by vaccination and vector control
Direct Contact Disease
Acquired immune deficiency syndrome (AIDS)

Caused by human immunodeficiency virus (HIV), a lentivirus within the family
Retroviridae
Believed to have evolved in Africa from viruses that infect other primates Disease occurs worldwide, but certain groups are more at risk
Homosexual/bisexual Intravenous Transfusion Prostitutes Newborn
men
drug users patients and hemophiliacs
children of infected mothers
Virus is acquired by direct exposure of the persons bloodstream to body fluids
containing the virus; can also be transmitted via breast milk

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Virus targets CD4+ cells such as T-helper cells, macrophages, dendritic cells, and
monocytes
Precise mechanism of pathogenesis is unknown Four types of pathological changes
AIDS-related
complex (ARC) - mild fever, weight loss, lymph node enlargement, and presence of antibodies to HIV; can develop to full-blown AIDS - antibodies not sufficient to prevent infection
Virus
AIDS
establishes itself in CD4 immunocompetent cells, which then proliferate in the lymph nodes and cause the lymph nodes to collapse to depletion of T-cell progenitors, which cripples the immune system the person open to opportunistic infections
Leads
Leaves
AIDS
dementia and other evidence of central nervous system damage; the virus can cross the blood-brain barrier cancer of the mouth and rectum,
Kaposis
AIDS-related
sarcoma (caused by human herpesvirus 8; HHV-8)
Carcinoma B-cell
lymphomas
Diagnosis is by viral antigen detection or by viral antibody detection
(seroconversion)
Three types of antiviral agents are used to treat HIV disease
Nucleoside
analogues that inhibit HIV reverse transcriptase (RT) inhibitors of HIV RT
Nonnucleoside Inhibitors
of HIV protease
Vaccines to stimulate production of neutralizing antibodies are currently under
investigation
Prevention and control involves screening of blood and blood products, education,
and protected sexual practices (use of condoms)

Ultimate Protection Against AIDS:
DONT BE STUPID!!!!!!
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Cold sores - fever blisters, herpes labialis

Caused by herpes simplex type 1 (HSV-1), a dsDNA virus Transmission is by direct contact Blister at site of infection is due to viral- and host-mediated tissue destruction Lifetime latency is established when virus migrates to trigeminal nerve ganglion 70-90% of U.S. adults have been infected Virus is periodically reactivated in times of physical or emotional stress Herpetic keratitis - recurring infections of the cornea that can result in blindness Drugs are available that are effective against cold sores, but treatment is mostly
supportive
Diagnosed by cell culture and immunological tests
Common cold (coryza)

Caused by many different rhinoviruses as well as other viruses Many do not confer durable immunity Understanding rhinovirus structure has suggested approaches to developing
vaccines and drugs

At one time, common cold was thought to be spread by explosive sneezing, but
now it is believed to be primarily spread by hand-to-hand contact

Treatment is supportive
Cytomegalovirus (CMV) inclusion disease

More than 80% of U.S. adults older than 35 years have been exposed to CMV and
carry a lifelong infection

Most infections are asymptomatic but infection can be serious in immunologically
compromised individuals
Virus persists in the body and is shed for several years in saliva, urine, semen,
and cervical secretions

Infected cells have intranuclear inclusion bodies Diagnosis is by viral isolation and serological tests Some antiviral agents are available for treatment, but only used in high-risk
patients
Prevention
Avoiding
close personal contact with infected individual
Use blood/organs from seronegative donors
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Genital herpes
Caused by herpes simplex type 2 (HSV-2), a dsDNA virus that is a member of
Herpesviridae
Virus is most frequently transmitted by sexual contact Disease has active and latent phases
Active
phase rapidly reproduces
Virus
Patient
can be symptom free or painful blisters in the infected area may occur, as well as other symptoms (fever, burning sensation, genital soreness heal spontaneously
Blisters
Latent
phase - after resolution of active phase virus retreats to nerve cells where the viral genome resides in the nuclei of host cells and can be periodically reactivated
Congenital (neonatal) herpes is spread to an infant during vaginal delivery;
therefore, infected females should deliver children by caesarean section

Estimated that 20% of U.S. adult are infected with HSV-2 There is no cure, but acyclovir decreases healing time, duration of viral shedding,
and duration of pain
Leukemia
Certain leukemias (adult T-cell leukemia and hairy-cell leukemia) are caused by
retroviruses (HTLV-1 and HTLV-2, respectively) and are spread similarly to AIDS
Often fatal and there is no effective treatment, although interferon has shown
some promise
Mononucleosis (infectious)
Caused by the Epstein-Barr virus (EBV), a herpesvirus (dsDNA virus) Spread by mouth-to-mouth contact (kissing disease) or by shared bottles and
glasses
Virus replicates in lymphatic tissue, eventually infects B cells, and causes
enlargement of lymph nodes and spleen, sore throat, headache, nausea, general weakness, and a mild fever
Disease is self-limited About 8% of college students contract mononucleosis Treatment is largely supportive and requires plenty of rest Diagnosis is made by serological tests 80-90% of adults worldwide are infected
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EBV is also associated with Burkitts lymphoma and nasopharyngeal carcinoma in
certain parts of the world
Rabies
Caused by a number of different strains of neurotropic viruses of the family
Rhabdoviridae (negative-strand RNA viruses)

Transmitted by bites of infected animals, aerosols in caves where bats roost, or by
scratches, abrasions, open wounds, or mucous membranes contaminated with saliva of infected animals
Virus multiplies in skeletal muscle and connective tissue, then migrates to central
nervous system, causing a rapidly progressing encephalitis

Diagnosis
Past
- presence of Negri bodies (masses of virus particles or unassembled viral subunits) - immunological tests, virus isolation, as well as the detection of Negri bodies
Today
Rabies cases in the U.S.

Humans Animals
- about 10 per year - about 8,000 per year
Symptoms progress and death results from destruction of the part of the brain that
regulates breathing
Vaccines conferring short-term immunity are available and must be given soon
after exposure (post exposure vaccination is effective because of the long incubation period of the virus)
Prevention and control
Annual Post
preexposure vaccination of dogs and cats preexposure vaccination of humans at special risk
exposure vaccination of humans
Frequent
Viral hepatitis
Hepatitis is any inflammation of the liver
Currently
eleven viruses are recognized as causing hepatitis CMV and EBV - do not cause permanent liver damage
Herpesviruses Nine
hepatotropic viruses
Some
have not been well characterized
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Hepatitis B (serum hepatitis)
Caused Virus
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by hepatitis B virus (HBV), a dsDNA virus with a circular genome transfusions equipment needles
is transmitted by
Blood
Contaminated Unsterile Any Also
body secretion transplacental transmission to fetus occurs
Three
42
distinct particles
nm spherical particle containing DNA and DNA polymerase (Dane particle) - infectious form or filamentous form 22 nm particle
Tubular
Spherical
Three
42
distinct particles
nm spherical particle containing DNA and DNA polymerase (Dane particle) - infectious form or filamentous form 22 nm particle
Tubular
Spherical
The
latter two forms are unassembled Dane particles and carry the hepatitis B surface antigen (HBsAg) that is used
As
a indicator of HBV screening of blood for vaccine development using recombinant DNA technology per year in the U.S. of HBV infection per year die of cirrhosis of the liver per year die from liver cancer
For
Basis
Cases
300,000 5,000 1,000 200
million people per year infected worldwide
Most
cases are asymptomatic; sometimes fever, appetite loss, abdominal discomfort, nausea, and fatigue develop; death can result from liver cirrhosis or HBV-related liver cancer
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Control
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measures involve contact with contaminated materials of high-risk groups immunotherapy within seven days of exposure
Excluding Passive
Vaccination
Hepatitis C
Caused Virus
by hepatitis C virus (HCV), an ssRNA virus within the family Flaviviridae is spread by contact with virus-contaminated blood route utero from mother to fetus transplants is by serological tests
Intimate In
Fecal-oral Organ
Diagnosis Has
reached epidemic proportions (leading cause of liver transplantations) with interferon
Treated
Hepatitis D
Is caused by hepatitis D virus (HDV) (formally called the delta agent), which only causes disease if the individual is coinfected with hepatitis B virus Coinfection may lead to a more serious acute or chronic infection than that normally seen with HBV alone Diagnosis is by serological tests Treatment is difficult and often involves administration of alpha interferon Prevention and control is by the use of the hepatitis B vaccine
Recently, hepatitis F and hepatitis G have been identified and are currently being
investigated Food-Borne and Waterborne Diseases Gastroenteritis (viral)-acute viral gastroenteritis Caused by Norwalk and Norwalk-like viruses, rotaviruses, caliciviruses, and astroviruses Main transmission route is fecal-oral route Disease is leading cause of childhood death in developing countries (5-10 million deaths/year) Seen most frequently in infants Causes 30-40% of infectious diarrhea cases in the U.S. with 75-150 deaths per
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BIOL 3702 Lecture Outline year
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Disease severity may range from asymptomatic infection, to mild diarrhea, to
severe and occasionally fatal dehydration

Viral gastroenteritis is usually self-limited Treatment is supportive
Hepatitis A - caused by the hepatitis A virus (HAV)

Spread by fecal contamination of food or drink, or by infected shellfish that live in
contaminated water
Caused by the hepatitis A virus (HAV), a plus-strand RNA virus of family
Picornaviridae
Mild intestinal infections sometimes progress to liver involvement Most cases resolve in four to six weeks and produce strong immunity Control is by hygienic measures and sanitary disposal of excreta A killed vaccine (Havrix) is now available and recommended for travelers to areas
of high morbidity due to HAV
Hepatitis E
Implicated in many epidemics in developing countries in Asia, Africa, and Central
and South America

Caused by hepatitis E virus (HEV), an ssRNA virus Infection is associated with fecal-contaminated drinking water HEV, like HAV, usually runs a benign course and is self-limiting Can be fatal (10%) in pregnant women in their last trimester There are no specific measures for prevention other than those aimed at
improving the level of health and sanitation in affected areas
Poliomyelitis

Caused by poliovirus, a member of the family Picornaviridae Plus-strand RNA virus that is stable and remains infectious in food and water

Once ingested, virus multiplies in throat and intestinal mucosa Subsequently enters bloodstream and causes viremia (99% of viremia cases are transient with no clinical disease) Can enter central nervous system (less than 1% of cases), leading to paralysis
Vaccines have been extremely effective (less than 10 cases per year; no
endogenous reservoir) in preventing and controlling the disease

Salk
vaccine (1952) - formalin-inactivated polio viruses (IPV); licensed in 1955 vaccine (1960s) - live, attenuated polio viruses given orally (OPV);
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Sabin
BIOL 3702 Lecture Outline licensed in 1962

Global eradication may be possible in the next few years
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Slow Virus and Prion Diseases
Progressive pathological process caused by a virus or a prion that remains clinically

silent for months or years
Followed by progressive clinical disease Ends in profound disability or death
Four of the six recognized human diseases are caused by prions termed spongiform
encephalophathies
Four more notable prion diseases

Cruetzfeldt-Jakob disease (CJD) Gerstamann-Strausler disease Fatal familial insomnia Kuru
Two newly-discovered forms of CJD

New-variant CJD (vCJD) - mad cow disease Iatrogneic CJD - medically induced by contaminated hormones or brain grafts
Other Diseases Diseases that do not fit into any of the previous categories Diabetes mellitus Viral arthritis Warts Warts Caused by different types of human papillomaviruses (HPVs) Infection limited to the skin and mucous membranes
Spread by direct contact between people and autoinoculation Four major types of worts
Plantar Verrucae Flat
vulgaris condylomata (veneral) transmitted

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(plane)
Anogenital
Sexually Play
a major role in the pathogenesis of epithelial cancers of the male and
BIOL 3702 Lecture Outline female genital tracts (90% of cervical cancer caused by HPV)
Treatment involves removal of warts
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Chapter 38: Human Diseases Caused by Viruses

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Chapter 38: Human Diseases Caused by Viruses

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