1971 Licensure of combined measles-
- Efficacy 95% (range, 90%-98%)
- Should be administered with mumps and rubella as MMR
Section II - Virology By Dr. Kareem Lilo
• First dose of MMR at 12-15 months
• Second dose of MMR at 4-6 years
• Second dose may be given any time >4 weeks after the first dose
• Rhabdovirus family; genus Lyssavirus
• Enveloped, bullet-shaped virions(Figure 2-36)
• Slow, progressive zoonotic disease
• Primary reservoirs are wild mammals; it can be spread by both wild and domestic mammals
by bites, scratches, and inhalation of droplets.
• Virus enters through bite, grows at trauma site for a week and multiplies, then enters nerve
endings and advances toward the ganglia, spinal cord and brain.(Figure 2-37)
• Infection cycle completed when virus replicates in the salivary glands (Figure 2-38)
• Prodromal phase – fever, nausea, vomiting, headache, fatigue; some experience pain,
burning, tingling sensations at site of wound
• Furious phase – agitation, disorientation, seizures, twitching, hydrophobia
• Dumb phase – paralyzed, disoriented, stuporous
Figure (2-36) Enveloped bullet shaped Rubies virus
Section II - Virology By Dr. Kareem Lilo
• Progress to coma phase, resulting in death
Figure (2-37) Rote spread of virus
Figure(2-38) Rabies virus inoculation and replication in infected person
Section II - Virology By Dr. Kareem Lilo
Rabid or suspected rabid animals are killed and examined by histopathology for Negri bodies and
• Vaccination of pets is required by law in most states
- First one developed by Pasteur by using spinal cords from infected dogs
- Today’s principal vaccine is the human diploid cell vaccine (HDCV) made in the WI-38
- One dose of hyperimmune antiserum
- Five immunizations over 28 days
Recommended prophylaxis in exposed individuals not previously vaccinated against rabies
• Diseased dog: viral antigen and Negri body in brain tissue (Figure2-39).
• Immediate thorough cleansing of all wounds with soap and
- should be infiltrated in wound(s)
- The remainder should be given IM
at a site distant from vaccine
IM (1 mL) in the deltoid area on days 0, 3, 7, 14, and 28
Section II - Virology By Dr. Kareem Lilo
ORTHOMYXOVIRUSES (Figure 2-40)(Figure2-41)
influenza types A,B,C (Figure 2-42)
febrile, respiratory illness with systemic symptoms
Figure(2-40) Orthomyxoviruses structure
Figure (2-39) (A,B) Negri body brain tissue
Section II - Virology By Dr. Kareem Lilo
Wild aquatic birds are the main reservoir of influenza A viruses. Virus transmission has been
reported from wield waterfowl to poultry, sea mammals, pigs, horses, and humans. Viruses are
also transmitted between pigs and humans, and from poultry to humans. Equine influenza
viruses have recently been transmitted to dogs. (From Fields Vriology (2007) 5th edition, Knipe,
Figure (2-42)Influenza virus nomenclature
Figure(2-43) Influenza A reservoir
Section II - Virology By Dr. Kareem Lilo
DM & Hawley, PM, eds, Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia Figure(2-
• Required for virus binding to cell surface sialyloglygolipids and sialyloglygoproteins.
• Responsible for virus penetration.
• Antibodies to HA neutralize virus.
• Cleavage to HA1 and HA2 required for infectivity.
1. Lowest homology is 25% (H1 and H3)
2. Highest homology is 80% (H2 and H5)
3. Less than 10% variation within subtype(Figure 2-44).
- Removes sialic acid from any glycoconjugate.
Figure(2-44) structural and non-structural coding by influenza virus genome
Section II - Virology By Dr. Kareem Lilo
- May remove “decoy” receptors on irrelevant cells during infection
- Prevents virus clustering at cell surface upon release
- High concentration of anti-NA antibody are necessary for virus neutralization(Figure 2-45).
Different species harbor different strains of the flu virus:
Figure(2-45)Influenza replication
Section II - Virology By Dr. Kareem Lilo
Influenza A virus: HA subtypes
Figure(2-46) NA subtypes in different animal species
Table(2-3) Influenza A virus : HA subtypes
Section II - Virology By Dr. Kareem Lilo
Binds to cell surface carbohydrate - sialic acid
Can be present as part of glycoprotein or glycolipid
Specific requirement for 2-3 and 2-6 linkages gives different tropism for avian vs. human cells
Figure (2-47) Influenza A virus , receptor of AH
Binds to cell surface carbohydrate - sialic acid
Can be present as part of glycoprotein or glycolipid
Specific requirement for 2-3 and 2-6 linkages gives
different tropism for avian vs. human cells (pigs have both)
Figure(2-48) Influenza A virus: attachment
Section II - Virology By Dr. Kareem Lilo
• On the surface of influenza virus reside two major proteins; Haemagglutinin (HA) and
Neuraminidase (NA). Sixteen subtypes of HA (H1 to H16) and nine subtypes of NA (N1 to
N9) are recognized in aquatic birds.
• Death mostly occurs as a consequence of primary viral pneumonia or of secondary
respiratory bacterial infections, especially in patients with underlying pulmonary or
cardiopulmonary diseases which causes death in different outbreak time( Figure2-50).
Figure(2-49) Type A influenza cannot be eradicated
Figure(2-50) Eras of human Influenza A virus
Section II - Virology By Dr. Kareem Lilo
Viruses undergo genetic change by several mechanisms
• Genetic drift where individual bases in the DNA or RNA mutate to other bases.
• Antigenic shift is where there is a major change in the genome of the virus. This occurs as a
result of recombination(Figure2-51).
• Epidemic (seasonal) influenza which occurs annually and is attributable to minor changes in
genes that encode proteins on the surface of circulating influenza viruses. These are known
• Pandemic influenza which occurs when more significant changes in the influenza A virus
arises when human virus strains acquire genes from influenza viruses of other animal
species. When this happens, everyone in the world is susceptible to the new virus, and a
worldwide epidemic or pandemic can result.
• Influenza has 8 separate gene segments that encode 10 different proteins
• When a host cell is infected with two different influenza viruses, the progeny virus can be a
mixture of both “parent” viruses
Figure(2-51)Antigenic variation of influenza virus envelope proteins
Section II - Virology By Dr. Kareem Lilo
• Reassortment provides for increased biological variation that increases the ability of the virus
to adapt to new hosts (figure 2-51) which result a pandemic influenza (Figure 2-53)
Figure(2-52)genetic mutation of influenza A-Antigenic drift B-Antigenic shift
Section II - Virology By Dr. Kareem Lilo
• Avian influenza is an infectious disease of birds caused by type A strains of the influenza
• These viruses occur naturally among wild aquatic birds worldwide and can infect domestic
poultry and other bird and animal species. The disease, which was first identified in Italy
• Fifteen subtypes of influenza virus are known to infect birds, thus providing an extensive
reservoir of influenza viruses potentially circulating in bird populations.
• H5N1; the strain of avian flu known as has been behind outbreaks of deadly avian flu.
• Migratory water birds, especially wild ducks. They may do not show clinical disease. The
virus colonizes the intestinal tract and is spread in the feces . They act as a reservoir for the
• Pigs can be infected by bird influenza (as well as by the form of influenza that affects
humans) and can pass on the flu to humans.
Figure(2-53) Generation of pandemic influenza virus strains
Section II - Virology By Dr. Kareem Lilo
- Influenza in swine was first recognized as an epizootic disease in 1918.
- Swine influenza virus was first isolated from humans in 1974. Serologic evidence of
infections with a swine influenza virus in humans has also been obtained. Viruses of swine
may be a potential source of epidemic disease for humans.
- Avian influenza transmitted by birds usually through feces or saliva.
- Avian influenza is not usually passed on to humans, although it has been contracted by
people who have handled infected birds or touched surfaces contaminated by the birds.
• Swine influenza (swine flu) is a respiratory disease of pigs caused by type A influenza virus
that regularly cause outbreaks of influenza in pigs.
• Like human influenza viruses, there are different subtypes and strains of swine influenza
viruses. The main swine influenza viruses circulating in U.S. pigs in recent years are: H1N1
influenza virus, H3N2 virus, H1N2 virus.
Figure(2-54) Influenza virus: the immune response
Section II - Virology By Dr. Kareem Lilo
Vaccination before the start of influenza season
• Northern Hemisphere: October-November
• Southern Hemisphere: April-May
Trivalent: two current A strains and one current B strain.
For 2010 season (Figure 2-55)
• A/California/7/2009 (H1N1)–like virus
• A/Perth/16/2009 (H3N2)–like virus
• B/Brisbane/60/2008–like virus
Formalin fixed “wild type” virus approved for parenterally administered vaccination.
Live attenuated vaccine (“Flumist”)
Temperature sensitive recombinant bearing relevant HA and NA genes.
Must anticipate shift and drift in order to identify appropriate vaccine strain.
Figure(2-55) General steps for influenza vaccine production
Section II - Virology By Dr. Kareem Lilo
Hepatitis (Liver-Attacking) Viruses
Hepatitis A – fecal/oral, contaminated food, vaccine available
Hepatitis B – blood, semen, vertical (mother-child), vaccine available
Hepatitis C – blood (IV drug use, transfusion, organ donation, unsterile injecting equipment, sexual
Hepatitis D – survives only in cells co-infected with hepatitis B
Hepatitis E* – contaminated food or water, fecal/oral(Table 2-3)
*causes short-term disease and is not a chronic carrier state
Table (2-3)Characteristics of hepatitis viruses
Section II - Virology By Dr. Kareem Lilo
- Hepatitis B is caused by infection with the Hepatitis B virus (HBV), the prototype member of
- It has a circular DNA genome of 3.2 kb (Figure 2-56)
- Currently, eight genotypes (A−H) are identified by a divergence of >8% in the entire genom
• A Hepadnaviridae – partially double-stranded DNA virus
• HBsAg – stimulates protective antibodies, a marker for current infection
• HBcAg – localized within liver cells, identifies acute infection, anti-HBcAg persists for life
and is a marker of past infection
• HBeAG – a marker of active replication and infectivity
- Numerous antigenic components
- May retain infectivity for more than 7 days at room temperature
Section II - Virology By Dr. Kareem Lilo
- More than 350 million chronically infected worldwide
- Established cause of chronic hepatitis and cirrhosis
- Human carcinogen – cause of up to 80% of hepatocellular carcinomas
- More than 600,000 deaths worldwide in 2002
• Worldwide, HBV is the primary cause of liver cancer
1. For males, it is the third leading cause of cancer mortality
2. For females, it is the sixth leading cause of cancer mortality
• The incubation period from the time of exposure to onset of symptoms is 6 weeks to 6
• HBV is found in highest concentrations in blood and in lower concentrations in other body
fluids (e.g., semen, vaginal secretions, and wound exudates).
Figure(2-57) Geographic distribution of Hepatitis virus
Section II - Virology By Dr. Kareem Lilo
• HBV infection can be self-limited or chronic.
• In adults, only approximately half of newly acquired HBV infections are symptomatic, and
approximately 1% of reported cases result in acute liver failure and death.
• Hepatitis B is detected by looking for a number of different antigens and antibodies:
Hepatitis B surface antigen (HBsAg):
- A protein on the surface of HBV; it can be detected in high levels in serum during acute or
- The presence of HBsAg indicates that the person is infectious.
- The body normally produces antibodies to HBsAg as part of the normal immune response to
- HBsAg is the antigen used to make Hepatitis B vaccine.
Hepatitis B is detected by looking for a number of different antigens and antibodies:
Hepatitis B surface antibody (anti-HBs):
• The presence of anti-HBs is generally interpreted as indicating recovery and immunity from
• Anti-HBs also develops in a person who has been successfully vaccinated against Hepatitis
Total Hepatitis B core antibody (anti-HBc):
• Appears at the onset of symptoms in acute Hepatitis B and persists for life.
• The presence of anti-HBc indicates previous or ongoing infection with HBV in an undefined
Hepatitis B is detected by looking for a number of different antigens and antibodies:
IgM antibody to Hepatitis B core antigen (IgM anti-HBc):
• Positivity indicates recent infection with HBV (≤6 months).
• Its presence indicates acute infection.
Hepatitis B e antigen (HBeAg):
Section II - Virology By Dr. Kareem Lilo
• A secreted product of the nucleocapsid gene of HBV that is found in serum during acute and
• Its presence indicates that the virus is replicating and the infected person has high levels of
Hepatitis B is detected by looking for a number of different antigens and antibodies: (Table 2-4)
Hepatitis B e antibody (HBeAb or anti-HBe):
• Produced by the immune system temporarily during acute HBV infection or consistently
during or after a burst in viral replication.
• Spontaneous conversion from e antigen to e antibody (a change known as seroconversion) is
a predictor of long-term clearance of HBV in patients undergoing antiviral therapy and
indicates lower levels of HBV. (Figure 2-58)
Typical interpretation of serologic test results for hepatitis B virus infection
Section II - Virology By Dr. Kareem Lilo
Section II - Virology By Dr. Kareem Lilo
Chronic Hepatitis B virus infection :
- Chronic viremia(Figure 2-59)
- Responsible for most mortality
- Higher risk with early infection
Hepatitis B perinatal transmission :
If mother positive for HBsAg and HBeAg
- 90% of infected infants become chronically infected
Figure (2-59) Hepatitis B virus multiplication
Section II - Virology By Dr. Kareem Lilo
- 5% - 20% of infants infected
- 90% of infected infants become chronically infected
Global patterns of chronic HBV infection :
High (> 8%) : 45% of global population
- Lifetime risk of infection >60%
- Early childhood infections common
Intermediate (2%-7%):43% of global population
- Lifetime risk of infection 20%-60%
- Infections occur in all age groups
Low(<20%):12% of global population
- Lifetime risk of infection <20%
- Most infections occur in adult risk groups
Adult at risk for HBV infection :
- Sex partners of HBsAg-positive persons
- Sexual active persons not in a long – term , mutually monogamous relationship.
- Persons seeking evaluation or treatment for a sexually transmitted disease.
adults at Risk for HBV Infection
Figure (2-60) Risk of chronic HBV carriage by age of infection
Section II - Virology By Dr. Kareem Lilo
percutaneous or mucosal exposure to blood
- household contacts of HBsAg-positive person
- residents and staff of facilities for development disabled persons.
- Healthcare and public safety workers with risk for exposure to blood or blood-contaminated
- Persons with end-stage renal disease
- Persons with diabetes mellitus.
For acute infection, no medication is available; treatment is supportive.
For chronic infection, several antiviral drugs (adefovir dipivoxil, interferon alfa-2b, pegylated
interferon alfa-2a, lamivudine, entecavir, and telbivudine) are available.
- Persons with chronic HBV infection require medical evaluation and regular monitoring to
determine whether disease is progressing and to identify liver damage or hepatocellular
CDC’s national strategy to eliminate transmission of HBV infection includes:
1. Prevention of perinatal infection through routine screening of all pregnant women for
HBsAg and immunoprophylaxis of infants born to HBsAg-positive mothers and infants born
to mothers with unknown HBsAg status
3. Vaccination of previously unvaccinated children and adolescents through age 18 years
4. Vaccination of previously unvaccinated adults at increased risk for infection
Composition Recombinant HBsAg
Efficacy 95% ( Range , 80%-100%
Duration of Immunity 20 years or more
Booster doses not routinely recommended
Section II - Virology By Dr. Kareem Lilo
Enteroviruses are a genus of the picornavirus family which replicate mainly in the
Single stranded naked RNA virus with icosahedral symmetry
Unlike rhinoviruses, they are stable in acid pH
Capsid has 60 copies each of 4 proteins, VP1, VP2, VP3 and VP4 arranged with icosahedral
symmetry around a positive sense genome.
At least 71 serotypes are known: divided into 5 groups
5. Enteroviruses (more recently, new enteroviruses subtype have been allocated sequential
Poliovirus - first identified in 1909 by inoculation of specimens into monkeys. The virus was
first grown in cell culture in 1949 which became the basis for vaccines.
Coxsackieviruses - In 1948, a new group of agents were identified by inoculation into
newborn mice from two children with paralytic disease. These agents were named
coxsackieviruses after the town in New York State. Coxsackieviruses A and B were identified
on the basis of the histopathological changes they produced in Newborn mice and their
capacity to grow in cell cultures.
Echoviruses - were later identified which produced cytopathic changes in cell culture and
was nonpathogenic for newborn mice and subhuman primates.
More recently, new enterovirus types have been allocated sequential numbers (68 - 71).
Figure(2-61)Enterovirus Particles
Section II - Virology By Dr. Kareem Lilo
Table(2-5) Categories of Enteroviruses
Section II - Virology By Dr. Kareem Lilo
- 3 serotypes of poliovirus (1, 2, and3) but no common antigen.
- Have identical physical properties but only share 36-52% nucleotide homology.
- Humans are the only susceptible hosts.
- Polioviruses are distributed globally. Before the availability of immunization, almost 100% of
the population in developing countries before the age of 5.
- The availability of immunization and the poliovirus eradication campaign has eradicated
poliovirus in most regions of the world except in the Indian Subcontinent and Africa.
- Poliovirus is on course of being eradicated worldwide by the end of 2000 or 2001.
The incubation period is usually 7 - 14 days.
Following ingestion, the virus multiplies in the oropharyngeal and intestinal mucosa.
Figure(2-63)Pathogenesis of enterovirus infection
Section II - Virology By Dr. Kareem Lilo
The lymphatic system, in particular the tonsils and the Peyer's patches of the ileum are invaded and
the virus enters the blood resulting in a transient viraemia.
In a minority of cases, the virus may involve the CNS following dissemination. (Figure 2-63)
Section II - Virology By Dr. Kareem Lilo
Born in 1882 at Hyde Park, New York--now a national historic site--he attended Harvard
Universityand Columbia Law School. On St. Patrick's Day, 1905, he married Eleanor Roosevelt .
Following the example of his fifth cousin, President Theodore Roosevelt, whom he greatly admired,
Franklin D. Roosevelt entered public service through politics, but as a Democrat. He won election to
the New York Senate in 1910. President Wilson appointed him Assistant Secretary of the Navy, and
he was the Democratic nominee for Vice President in 1920 .
In the summer of 1921, when he was 39, disaster hit-he was stricken with poliomyelitis.
Demonstrating indomitable courage, he fought to regain the use of his legs, particularly through
swimming. At the 1924 Democratic Convention he dramatically appeared on crutches to nominate
Alfred E. Smith as "the Happy Warrior." In 1928 Roosevelt became Governor of New York .
He was elected President in November 1932, to the first of four terms.)Figure2-65)
Antibody is the major protective immune response to the enteroviruses . Secretory antibody
can prevent the initial establishment of infection in the oropharynx and gastrointestinal tract,
and serum antibody prevents viremic spread to the target tissue and therefore disease.
Cell-mediated immunity is not usually involved in protection but may play a role in
Figure(2-65)Franklin D. Roosevelt
Section II - Virology By Dr. Kareem Lilo
There are 3 possible outcomes of infection:
1. Subclinical infection (90 - 95%) - inapparent subclinical infection account for the vast
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