2. Abortive infection (4 - 8%) - a minor influenza-like illness occurs, recovery occurs within a
few days and the diagnosis can only be made by the laboratory. The minor illness may be
accompanied by aseptic meningitis
3. Major illness (1 - 2%) - the major illness may present 2 - 3 days following the minor illness or
without any preceding minor illness. Signs of aseptic meningitis are common. Involvement
of the anterior horn cells lead to flaccid paralysis. Involvement of the medulla may lead to
respiratory paralysis and death.
a. Mainstay of diagnosis of poliovirus infection
b. poliovirus can be readily isolated from throat swabs, faeces, and rectal swabs. It is rarely
c. Can be readily grown and identified in cell culture
d. Requires molecular techniques to differentiate between the wild type and the vaccine type.
- Very rarely used for diagnosis since cell culture is efficient. Occasionally used for immune
status screening for immunocompromised individuals.
No specific antiviral therapy is available. However the disease may be prevented through
vaccination. There are two vaccines available.
Intramuscular Poliovirus Vaccine (IPV)
consists of formalin inactivated virus of all 3 poliovirus serotypes.
Produces serum antibodies only: does not induce local immunity and thus will not prevent local
Section II - Virology By Dr. Kareem Lilo
Consists of live attenuated virus of all 3 serotypes.
Produces local immunity through the induction of an IgA response as well as systemic immunity.
Rarely causes paralytic poliomyelitis, around 1 in 3 million doses.
Most countries use OPV because of its ability to induce local immunity and also it is much
The normal response rate to OPV is close to 100%.(Figure2-64)
OPV is used for the WHO poliovirus eradication campaign.
Because of the slight risk of paralytic poliomyelitis, some Scandinavian countries have
reverted to using IPV. Because of the lack of local immunity, small community outbreaks of
poliovirus infections have been reported.
Poliovirus was targeted for eradication by the WHO by the end of year 2000 (now 2005). To
this end, an extensive monitoring network had been set up.
Poliovirus has been eradicated from most regions of the world except the Indian
subcontinent and sub-Saharan Africa. It is possible that the WHO target may be achieved.
Section II - Virology By Dr. Kareem Lilo
Coxsackieviruses are distinguished from other enteroviruses by their pathogenicity for
suckling rather than adult mice. They are divided into 2 groups on the basis of the lesions
- Group A viruses produce a diffuse myositis with acute inflammation and necrosis of fibers of
- Group B viruses produce focal areas of degeneration in the brain, necrosis in the skeletal
muscles, and inflammatory changes in the dorsal fat pads, the pancreas and occasionally the
Each of the 23 group A and 6 group B coxsackieviruses have a type specific antigen.
In addition, all from group B and one from group A (A9) share a group Ag. Cross-reactivities
have also been demonstrated between several group A viruses but no common group
The first echoviruses were accidentally discovered in human faeces, unassociated with
human disease during epidemiological studies of polioviruses. The viruses were named
echoviruses (enteric, cytopathic, human, orphan viruses).
These viruses were produced CPE in cell cultures, but did not induce detectable pathological
Altogether, There are 32 echoviruses (types 1-34; echovirus 10 and 28 were found to be other
viruses and thus the numbers are unused)
There is no group echovirus Ag but heterotypic cross-reactions occur between a few pairs.
Newly identified picornaviruses that are not polioviruses are no longer classified separated
into the species coxsackie and echovirus because of the ambiguities presented by
overlapping host range variations.
4 new enteroviruses have been identified (68 - 72). Enterovirus 70 is the causative agent
epidemics of acute haemorrhagic conjunctivitis that swept through Africa, Asia, India and
Europe from 1969 to 1974. The virus is occasionally neurovirulent.
Section II - Virology By Dr. Kareem Lilo
Enterovirus 71 appears to be highly pathogenic and has been associated with epidemics of a
Enterovirus 72 was originally assigned to hepatitis A virus, but it had now been assigned to a
new family called heptoviruses.
Paralytic Disease - most commonly associated with polioviruses but other enteroviruses
may also be responsible, notably enterovirus 71
Meningitis - caused by all groups of enteroviruses, most commonly seen in children under 5
Encephalitis - focal or generalized encephalitis may accompany meningitis. Most patients
recover completely with no neurological deficit.
Undifferentiated febrile illness - may be seen with all groups of enteroviruses.
Hand foot mouth disease - usually caused by group A coxsackieviruses although group B
coxsackieviruses and other enteroviruses have been caused outbreaks.
Herpangina - caused by group A coxsackieviruses.
Epidemic Pleurodynia (Bornholm disease) - normally caused by group B coxsackieviruses.
Myocarditis - group B coxsackieviruses are the major cause of myocarditis, although it may
be caused by other enteroviruses. It may present in neonates as part of neonatal infection and
is often fatal. In adults, the disease is rarely fatal.
Respiratory Infections - several enteroviruses are associated with the common cold.
Rubelliform rashes - a rash disease resembling rubella may be seen with several coxsackie
Neonatal Infection - some coxsackie B viruses and echoviruses may cause infection in
newborn infants. The virus is usually transmitted perinatally during the birth process and
symptoms vary from a mild febrile illness to a severe fulminating multisystem disease and
Conjunctivitis - associated with several types of enteroviruses, notably Coxsackie A24 and
Enterovirus 70 (haemorrhagic conjunctivitis)
Section II - Virology By Dr. Kareem Lilo
Pancreatitis/Diabetes - associated with Coxsackie B virus infection. The extent of the role of
the virus in diabetes is unknown.
Virus Isolation (Figure 2-67)
- Mainstay of diagnosis of enterovirus infection
- Coxsackie B and Echoviruses can be readily grown in cell culture from throat swabs, faeces,
and rectal swabs. They can also be isolated from the CSF
- Coxsackie A viruses cannot be easily isolated in cell culture. They can be isolated readily in
suckling mice but this is not offered by most diagnostic laboratories because of practical
considerations. Molecular techniques may provide a better alternative.
- Very rarely used for diagnosis since cell culture is efficient.
- Neutralization tests or EIAs are used but are very cumbersome and thus not offered by most
There is no specific antiviral therapy available against enteroviruses other than polio.
Some authorities use IVIG in the treatment of neonatal infections or severe infections in
immunocompromised individuals. However, the efficacy is uncertain.
HNIG have been to prevent outbreaks of neonatal infection with good results.
developing a vaccine except against enterovirus 71 and coxsackie B viruses.
Section II - Virology By Dr. Kareem Lilo
Adenoviruses were first isolated in 1935 from human adenoid tissues.
Since then, at least 49 distinct antigenic types have been isolated from humans and many
All human serotypes are included in a single genus within the family Adenoviridae.
All human Adenoviruses share a common group-specific antigen.
- Type specific antigens are important in serotyping.
- Adenoviruses have a characteristic morphology (Stewart et al., 1993 ), with an icosahedral
capsid consisting of three major proteins, hexon (II), penton base (III) and a knobbed fiber
(IV), along with a number of other minor proteins, VI, VIII, IX, IIIa and IVa2 .The virus
Figure(2-68) Adenovirus structure
Section II - Virology By Dr. Kareem Lilo
genome is a linear, double-stranded DNA with a terminal protein (TP) attached covalently to
the 5´ termini (Rekosh et al., 1977)
Adenoviruses are divided into six groups (A to F) based on:
- Antigenic structure divides adenoviruses into:
About 1/3 of the 49 known human serotypes are responsible for most cases of Adenovirus
Adenoviruses infect and replicate in the epithelial cells of the:
Figure(2-69) Adenovirus Attachment
Section II - Virology By Dr. Kareem Lilo
They usually do not spread beyond the regional lymph nodes EXCEPT IN THE IMMUNE
The virus has a tendency to become latent in lymphoid tissue,
The virus can be reactivated by immunosuppression.
Adenoviruses cause primary infection in:
Several distinct clinical syndromes are associated with Adenovirus infection.
e. Adenoviral infections of the immune compromised host
The most important etiological association of adenoviruses is with the respiratory diseases.
They are responsible for 5% of acute respiratory diseases in:
Two serotypes (40, 41) have been etiologically associated with infantile gastroenteritis.
Section II - Virology By Dr. Kareem Lilo
Virus particle by EM can be detected by direct examination of fecal extracts.
Detection of adenoviral antigens by ELISA.
Detection of adenoviral NA by Polymerase chain reaction: can be used for diagnosis of
Adenovirus infections in tissue samples or body fluids.
Isolation depending on the clinical disease, the virus may be recovered from throat, or
conjunctival swabs or and urine.
Isolation is much more difficult from the stool or rectal swabs
Section II - Virology By Dr. Kareem Lilo
1. Haemagglutination inhibition
2. Neutralization tests can be used to detect specific antibodies following Adenovirus infection.
1. Careful hand washing is the easiest way to prevent infection.
2. Disinfection of Environmental surfaces with hypochlorites.
3. The risk of water borne outbreaks of conjunctivitis can be minimized by chlorination of
4. Epidemic keratoconjunctivitis can be controlled by strict asepsis during eye examination.
Section II - Virology By Dr. Kareem Lilo
8.Human Immunodeficiency Virus
- H = Infects only Human beings
- I = Immunodeficiency virus weakens the immune system and increases the risk of infection
- V = Virus that attacks the body
Acquired Immune Deficiency Syndrome
- I = Weakens the Immune system
- D = Creates a Deficiency of CD4+ cells in the immune system
- S = Syndrome, or a group of illnesses taking place at the same time
When the immune system becomes weakened by HIV, the illness progresses to AIDS
Some blood tests, symptoms or certain infections indicate progression of HIV to AIDS
- Transmitted through the same routes
- Associated with similar opportunistic infections
HIV-1 is more common worldwide
HIV-2 is found in West Africa, Mozambique, and Angola
o HIV-2 is less easily transmitted
1. Direct contact with infected blood
2. Sexual contact: oral, anal, or vaginal
3. Direct contact with semen or vaginal and
Section II - Virology By Dr. Kareem Lilo
5. HIV-infected mothers to infants during
6. pregnancy, delivery, or breastfeeding
RNA virus discovered in 1983
Virus binds to specific CD4 receptor sites and then enters the cell
- Virus enters the cell nucleus
- Using integrase the virus splices itself into genome to become part of the cell’s genetic
•It is a retrovirus with two copies of single stranded RNA genome
•It uses reverse transcriptase to transform its ss-RNA genome into a ds-DNA for integration into its
Figure(2-71)HIV-1 Virus structure
Section II - Virology By Dr. Kareem Lilo
•It has marker proteins (gp120) in the protein coat that allow it to recognize specific cells in the
•The protein coat also contains MHC-I and MHC-II molecules
gag gene codes for nucleocapsid proteins
env gene codes for envelope glycoproteins, i.e. gp41 (transmembrane protein) and gp120
pol gene codes for enzymes such as reverse transcriptase, protease and integrase (Figure 2-
Other genes code for various activators and accessory proteins
HIV destroys CD4+ cells 3 ways
1. Viral replication leaves holes in cell membranes
2. Infected cells fuse with other cells
Combine to form a syncytium that destroys all affected cells .
3. Antibodies against HIV bind to the infected cells and activate the complement system, which
- All daughter cells from infected cell are infected
- Genetic codes can direct the cell to make HIV
Section II - Virology By Dr. Kareem Lilo
- Viremia (large amount of virus in blood)
- Steady state of viral load can be maintained for many years
• HIV destroys about 1 billion CD4+ T cells every day
• Immune problems start when CD4+T cell counts drop below 500 cells/μl
• While CD4 is recognized by the virus, it is not sufficient for viral attack; it needs a
• T cells: coreceptor is CXCR4, which also acts as a receptor for the chemokine SDF-1; there
is competitive inhibition between chemokine and HIV for binding; the HIV strain is
• Monocytes: coreceptor is CCR5, which is a receptor for chemokines, which also act as
competitive inhibitors to HIV; the HIV strain is called M-tropic
• T-tropic HIV strains cause syncytia: formation of giant cells as a result of fusion of cells via
the gp120 protein on viral coats.(Figure2-73)
Figure(2-73) Complete Activation of HIV
Section II - Virology By Dr. Kareem Lilo
Infection of Human Cell with HIV
• HIV gp120 surface protein binds CD4 on target cell
• Transmembrane component, gp41, binds coreceptor
• Viral genome and other proteins are able to enter the
• RT transcribes the ssRNA genome
• The next DNA strand is made, making a double
stranded DNA molecule called a provirus
• The dsDNA is transferred to the nucleus to be added to
the host genome via the viral integrase protein at HIV
Figure(2-73)Infection of Human Cell with HIV
• In a latent cell, the integrated provirus must be activates
by transcriptional factors to make genomic ssRNA and
• Host ribosomes transcribe viral mRNAs, and the proteins
are either with the genomic RNA or part of the membrane
• The membrane buds to form a viral envelope
• The mature virus is released outside the cell
• These latent cells are dangerous because they can remain
latent for long periods of time(Figure 2-75)
Figure(2-75)Activation of Provirus
Section II - Virology By Dr. Kareem Lilo
Progression from HIV infection to stage of AIDS (figure 2-76)
WINDOW PERIOD (3-12 weeks or even 6 months)
(Antibodies to HIV not yet developed, test does not capture the real status but person can infect
(Development of antibodies, can be detected in test)
Figure(2-76)Progression of HIV to AIDS
Section II - Virology By Dr. Kareem Lilo
No exclusive symptoms (mild fever or flu like features in some cases)
May take up to 10 to 12 years to reach the stage of AIDS, the period can be prolonged through
• Tests should be taken 12 weeks after high-risk behavior, repeated 6 months after an
A. ELISA: enzyme-linked immunosorbent assay
B. Western Blot: rechecks ELISA results
C. Viral load tests measure HIV in bloodstream (PCR)
Major Signs / Symptoms of AIDS:
1. Weight loss (> 10% of body weight)
2. Fever for longer than a month
3. Diarrhea for longer than a month
2. General itchy skin diseases
4. Recurring shingles (herpes zoster)
5. Long lasting, spreading and severe cold sores
6. Long lasting swelling of the lymph glands
8. Loss of intellectual capacity
• Nonnucleoside reverse transcriptase inhibitors
• Nucleoside reverse transcriptase inhibitors
Section II - Virology By Dr. Kareem Lilo
- HAART – Highly Active Antiretroviral Therapy
• Combination of three or more medications
- Atripla – newest antiretroviral
• Combination of three medications in one pill
• Lowers the amount of HIV (called viral load) by interfering with the way HIV makes copies
3Points In HIV Cell Cycle Where Replication Can be Stopped
• Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
• Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
• All 3 of these treatments are usually prescribed at once. Known as HAART, the combination
of all 3 fights the ability of the virus to rapidly mutate.(Figure 2-77)
Reverse Transcriptase Inhibitors
• Reverse Transcriptase Inhibitors interfere with the reverse transcriptase (RT) enzyme that
HIV needs to make copies of itself. There are 2 types of inhibitors each working differently .
Figure (2-77) 3Points In HIV Cell Cycle Where Replication Can be Stopped
Section II - Virology By Dr. Kareem Lilo
Type 1: NRTI’s – nucleoside drugs provide faulty DNA building blocks, stopping the DNA chain
the virus uses to make copies of itself .
Type 2: NNRTI’s- non-nucleoside RT inhibitors bind RT so the virus cannot carry out its copying
Examples Include: AZT, 3TC, Combivir, Nevirapine
• Protease Inhibitors (PI), discovered in 1995, block the protease enzyme. When protease is
blocked, HIV makes copies of itself that can’t infect new cells .
• PI Side Effects: PI’s can cause high blood sugar and consequently diabetes. Another main
concern is lipodystrophy, where your body absorbs fats and nutrients in an irregular
manner. Latent HIV can hide out in these fat cells .
Can HIV be Vaccinated Against?
- HIV thrives in the presence of circulating antibodies directed against it .(Figure 2-78)
- HIV integrates itself into the host genome and may stay dormant for years. All retroviruses
- HIV mutates and can show up to 109 viruses per day, while the common cold with 100
subtypes has proven to difficult to make a vaccine for
Figure(2-78)HIV vaccine challenge agent
Section II - Virology By Dr. Kareem Lilo
• Care and concern about HIV and AIDS for those who are living with HIV, for those who are
ill, for those who have died and for those who care for and support those directly affected.
• Hope - that the search for a vaccine and cure to halt the suffering will be successful.(Figure 2-
• Support for those living with HIV, for the continuing education of those not infected, for
maximum efforts to find effective treatments, cures or vaccines, and for those who have lost
friends, family members or loved ones to AIDS.
Section II - Virology By Dr. Kareem Lilo
Viruses contribute to development of some cancers. Typically, the virus can cause genetic changes in
cells that make them more likely to become transformed .
These cancers and viruses are linked
1. Cervical cancer and the genital wart virus, HPV
2. Primary liver cancer and the Hepatitis B virus
A-Carcinogenesis B-Factors in Carcinogenesis
Figure (2-80)Human causes by viruses
Section II - Virology By Dr. Kareem Lilo
3. T cell leukaemia in adults and the Human T cell leukaemia virus(Figure 2-80)
- Diploid single-stranded RNA viruses (5-8 kb)
- Icosahedral symmetry (100 nm)
Table (2-5) Viruses Associated With Human Cancers
Section II - Virology By Dr. Kareem Lilo
Genes encoded in both directions
o Typical infectious viruses (exogenous)
- Other, unknown transmission mechanisms
o Nontransforming retroviruses
Mechanisms of Retroviral Carcinogenesis
Infection leads to uncoating in the cytoplasm
Reverse transcriptase makes a double-stranded DNA copy
The ds-DNA translocates into the nucleus where it randomly integrates in host cell
This version of the viral genome is termed the provirus
- Induce cell division - leads to copies of the viral genome in each daughter cell
- Productive infection - spread of virus to other cells.
Section II - Virology By Dr. Kareem Lilo
- Nonenveloped icosahedral (55 nm)
- Stimulate cellular DNA synthesis
- Highly restricted host range and tissue range
Only a few are known to cause cancers
Cervical cancer is the most important
Vaccine is now available (Gardasil; types 6, 11, 16, 18)
Section II - Virology By Dr. Kareem Lilo
Cause warts (abnormal cellular proliferation)
Replicate in basal stem cells and keratinocytes of the skin and mucosa
- HeLa cells are cervical cancer cells from Helen Lang (fatal)
Papillomaviruses Encode Two Structural Proteins
Region of greatest genetic conservation
- Capsid is 72 pentamers of L1
- Expressed L1 assembles into viral conformation, viral-like particles (VLPs)
L2 is minor capsid protein(Table 2-7)
Required for encapsidation of viral genome(Figure 2-82)
L1: the major structural protein. Each viral particle has 360 copies in 72 pentamers.
L2: the minor structural protein. Up to 72 copies per particle.(Figure2-81)
Figure (2-81) Papillomavirus Particle
Section II - Virology By Dr. Kareem Lilo
Table (2-8) Papilloma virus gene function
Section II - Virology By Dr. Kareem Lilo
HPV DNA integration and cervical carcinoma
Strong association between integrated HPV DNA and cervical carcinoma. (HPV-16, HPV-18,
DNA integration anywhere in chromosome
Integration upregulates E6 and E7 gene expression
Disrupts E2 function: loss transcriptional repression of E6 and E7
E6 and E7 expressed in cells from cervical carcinoma
Binds Rb (a cellular anti-oncogene), releasing E2F (a cellular transcription factor)
E6 cooperates in transformation
Stimulates degradation of p53 (a cellular anti-oncogene, transcription factor)
Unregulated expression of HPV E6 and E7 results in unregulated cell cycling (Figure 2-84)
Figure (2-84) Precursor lesions for cervical cancer
Section II - Virology By Dr. Kareem Lilo
There are no tests to detect the HPV virus.
Most people who contract HPV will never know they have it.
Having HPV does not mean you have a disease – most people don’t have any signs or
Some low risk types cause genital and anal warts.
In rare instances, the virus persists, especially the high risk types of the HPV virus that can
develop pre-cancerous lesions and cancer.(Figure2-85)(Figure2-86)(Figure2-87).
1. Absolutely no skin-to-skin sexual contact.
2. One sexual / intimate partner forever.
3. The more sexual partners, the higher the chance of contracting HPV.
4. Using condoms is excellent protection against STI, but does not cover all the skin.
5. Pap testing will detect abnormal cells.(Figure 2-88)
6. Vaccination is now available to prevent certain low risk types that cause genital warts certain
high risk types that cause cancer.
Figure(2-90) HPV Infection and Cervical Cancer
Section II - Virology By Dr. Kareem Lilo
Figure(2-87)Cervical Cancer Develop at the Transition Zone Between Squamous and Columnar Epithelium
Figure(2-86)HIV infection and cervical cancer
Section II - Virology By Dr. Kareem Lilo
Two Distinct HPV VLP Vaccines Were Developed Commercially
ASO4 Adjuvant (Aluminum + MPL)
Figure(2-88) Cervical oncogenes and cellular tumor suppressor genes in cervical cancer
Section II - Virology By Dr. Kareem Lilo
IM Injections at 0, 1 or 2, and 6 months
Prophyactic HPV Vaccines Are L1 Virus Like Particles (VLPs(
of virion neutralizing antibodies
Figure (2-89) Cervical cancer vaccine preparation
Section II - Virology By Dr. Kareem Lilo
Live Attenuated Viruses Are Not Suitable For an HPV Prophylactic Vaccine
Papillomavirus cannot be efficiently
The viral genomes contain oncogenes
Virion protein-based subunit vaccines
are preferable, if they could efficiently induce neutralizing antibodies .
The strongest evidence linking EBV and cancer formation is found in Burkitt's lymphoma
and Nasopharyngeal carcinoma(Figure2-90)
form of skin cancer that can involve internal organs. It most often is found in patients with
acquired immunodeficiency syndrome (AIDS), and can be fatal )Figure 2-91)
Figure(2-90)EBV-associated indigence
Figure (2-91) Kaposite sarcoma
Section II - Virology By Dr. Kareem Lilo
cancer that arises from hepatocytes, the major cell type of the liver .
Hepatocellular carcinoma is one of the major cancer killers .
It affects patients with chronic liver disease who have established cirrhosis, and currently is
the most frequent cause of death in these patients .
The main risk factors for its development are hepatitis B and C virus infection, alcoholism
Section II - Virology By Dr. Kareem Lilo
A vaccine is any preparation intended to produce immunity to a disease by stimulating the
production of antibodies. Vaccines include, for example, suspensions of killed or attenuated
microorganisms, or products or derivatives of microorganisms.
The most common method of administering vaccines is by injection(Figure2-92), but some
are given by mouth or nasal spray.
- Haemophilus influenzae type b (Figure 2-94)
- Meningococcal disease (Figure 2-95)
Figure (2-92)vaccine administration by injection
Section II - Virology By Dr. Kareem Lilo
Figure (2-93) This child has diphtheria and has developed a pseudo-membrane, a thick gray coating
Figure(2-94) This child has a swollen face due to Hib infection.
Section II - Virology By Dr. Kareem Lilo
Caused by the bacterium Streptococcus pneumoniae
Can infect different parts of the body leading to:
2. Bacteremia (blood infection)
Figure(2-95) This 4-month-old has gangrene due to infection with meningococcus.
Figure(2-96) Child with broken blood vessels in eyes and bruising on
face due to severe coughing caused by pertussis.
Section II - Virology By Dr. Kareem Lilo
- Inactivated vaccines also ight viruses. These vaccines are made by
- inactivating, or killing, the virus during the process of making
- the vaccine. The inactivated polio vaccine is an example of this
- type of vaccine. Inactivated vaccines produce immune responses
- in different ways than live, attenuated vaccines. Often, multiple
- doses are necessary to build up and/or maintain immunity
Figure (2-98) This child was experiencing painful muscle spasms due to infection with tetanus.
Section II - Virology By Dr. Kareem Lilo
Figure(2-98) Importance of T helper cells in an immune response: T helper cells recognize antigens
from antigen-presenting cells (APCs) and then release cytokines and activate other immune cells.
Parasitic worms influence what kinds of T helper cells are activated.
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