Viruses are a major cause of infections in humans. Some important viruses discussed include herpesviruses like herpes simplex virus 1 and 2, varicella zoster virus, cytomegalovirus and Epstein-Barr virus. Hepatitis viruses and human papillomaviruses are also discussed. Herpesviruses can cause lifelong latent infections. Human papillomaviruses can transform cells and cause warts and cancers like cervical cancer. Influenza A viruses can cause pandemics in humans through antigenic shift.
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Medical Importance of Viruses
• Viruses are the most common cause of acute infections
• Several billion viral infections per year
• Some viruses have high mortality rates
• Possible connection of viruses to chronic afflictions of
unknown cause
• Viruses are major participants in the earth’s ecosystem
– Is it beneficial?
– Do viruses have additional benefits?
4. Some Important viruses you should know…
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• Smallpox (variola major, minor) – complex virus; inclusions
• Herpesviridae – (herpes; chicken pox – varicella zoster); chronic latent
state reactivated; nuclear inclusions
• HPV – can transform cells; warts cervical cancer
• Hepatovirus (A, B, C) – will be discussed latter
• Polio – enterovirus – enteric (oral vaccine)
• Cold (Rhinovirus) – antibiotics ineffective! It’s a virus!!
• West Nile – is a flavivirus; spread by moquitoes; bird is reservoir
• SARS – coronavirus (like the virus that causes bronchitis); prominent
spikes on envelope
• influenza – Flu; Type A is the one you’ve had;
• Rotavirus – viral food poisoning; vomiting and diarrhea – sometimes
concurrently!!
• HIV – retrovirus; latency; will be discussed latter
11. Herpes simplex viruses
Widespread
Broad host range
Grow rapidly & highly cytolytic
cause gingivostomatitis to keratoconjunctivitis,
encephalitis, genital disease & neonatal infections
Latency occur in nerve cells
Recurrences are common
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12. Two distinct viruses of HSV
HSV-1 and HSV-2
Genome is similar for both viruses
Cross react serologically
Two glycoproteins which are specific for each virus
Glycoprotein G1 (gG1) is specific for HSV-1
For HSV-2, gG-2 is specific
Mode of transmission is different
HSV-1 is transmitted by contact with saliva
HSV-2 is transmitted sexually / maternal to newborn
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Herpes simplex viruses
13. Pathogenesis & pathology
Causes necrosis with inflammation
Lesions of HSV-1and 2 are similar
Infected cells may show ballooning
Formation of Cowdry type A intranuclear inclusion bodies
In these inclusion bodies, there is marginated chromatin with multinucleated giant
cells
Cell fusion may enhance the spread of virus from one cell to other
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14. Primary infection
Acquired by contact especially on mucosa or broken skin
HSV-1 infects oropharynx and spread by respiratory droplets or saliva
HSV-2 is transmitted by genital routes
After entry, replication takes place at the site then the virus spread to local nerve
endings
Further spread to dorsal root ganglia and further undergo replication
HSV-1 latency is acquired in trigeminal ganglia
HSV-2 latency is obtained in sacral ganglia
Primary infections are mild and asymptomatic
Systemic disease may arise in case of immune compromised patients
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15. Latent infection
Infected ganglia virus occur in nonreplicating state
May last for life time of the patient
Axonal injury, fever, physical/emotional stress, U.V light
exposure may lead to reactivation
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16. Clinical syndromes
HSV-1 is a oropharyngeal disease especially affecting
children causing gingivitis
In adults it may cause pharyngitis, tonsillitis
Recurrence due to this virus may be formation of cluster of
vesicles at border of lips called cold sores
HSV-1 may also cause keratoconjunctivitis
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17. Genital Herpes
Mainly caused by HSV-2
But HSV-1 may also be responsible in case of oral sex
Primary genital infections are usually severe with painful
vesiculoulcerative lesions of penis or
cervix,vulva,vagina,perineum
Recurrence is mild with few vesicles
Recent reports says that HSV-2 is also associated with
cervical carcinoma in women
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18. Skin infections
By Abrasions HSV-1 and 2 can enter, it is called traumatic herpes
Lesions may occur in the fingers of dentists, hospital staff it is called
herpetic whitlow
Occur in the bodies of wrestlers called herpes gladiatorum
In eczema patients HSV-1 infections are very severe Eczema
herpeticum
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Encephalitis
19. Neonatal herpes
It is acquired in utero /
During birth / after birth
HSV-2 is transmitted by contact in the birth canal
Post natal infection is caused by both HSV-1&2
May form skin lesions, encephalitis and
disseminated disease
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20. Varicella-Zoster virus (HHV3)
Varicella (chickenpox)
mild , highly contagious disease, mainly affecting children
generalized vesicular eruption of the skin and mucous membranes
may be severe in adults and immunocompromized children
Zoster (shingles)
– sporadic , incapacitating disease of adults or immunocompromised
individuals
– rash limited in distribution of the skin innervated by a single sensory
ganglion
– the lesions are similar to those of varicella
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21. Both diseases are caused by the same virus
Varicella is the acute disease that follows primary contact with the virus
Zoster is the response of the partially immune host to reactivation of
varicella virus present in latent form in neurons in sensory ganglia
Varicella-Chicken pox
↓
Latency
↓
Zoster-Shingle
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DNA Viruses for PC -II
Varicella-Zoster virus
22. Pathogenesis
Varicella
- the route of infection is the mucosa of the URT or the conjunctiva
- circulates in the blood
- multiple cycles of replication
- localized in the skin
- cutaneous and mucosal lesions are initiated by viral infection of capillary
endothelial cells
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23. Zoster
waning immunity allows viral replication to occur in a ganglion, causing
intense inflammation and pain
travels down the nerve to the skin and induces vesicle formation
- skin lesions
identical to those of varicella
often only a single ganglion involved
lesions in the skin corresponds areas of innervation on dorsal root
ganglion
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Varicella-Zoster virus
25. Cytomegalovirus(HHV-5)
‘Large cell virus’
Swollen cells containing large intranuclear inclusions
Ubiquitous
CMV infection are 'slow' - 7-14 days
Chances for acquiring CMV are high
Poverty, overcrowding, poor hygiene will enhance
transmission
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26. CMV infections differ in terms of age of patients, mode of
transmission, clinical presentation
CMV is transmissible to fetus through placenta
Responsible for neonatal morbidity and mortality
Normal infants can acquire infection from colostrum or
breast milk
Young children liable to get infection by contaminated
urine and saliva
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Clinical Aspects
27. Cytomegalovirus Infections
Fetus From mother, across placenta
Infant Contact with maternal body fluids during birth, breast feeding
Young child Contact with urine / saliva of other children
Adults Kissing, sexual intercourse, blood transfusion
Transplant recipient Donated tissues, blood transfusion, reactivation due
to immunosuppression
In adults it may cause infectious mononucleosis (heterophil-negative)
like syndrome
CMV causes febrile illness with splenomegaly, impaired liver
function, jaundice, lymphocytosis, neurologic impairment
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28. Epstein-Barr virus (EBV) infections
It is associated with malignant disease
Infectious mononucleosis - adults - World wide
Burkitt’s lymphoma (BL) - 4 — 12 years - Endemic in sub-Saharan
Africa & New Guinea
Nasopharyngeal carcinoma - 20 – 50 -years - Endemic in south
China
B-cell lymphoma - Children and adults - Immunodeficient patients
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Epstein – Barr virus(HHV-4)
29. Pathogenesis
Initiates infection in the oropharynx
Replication occurs in epithelial cells of the pharynx and salivary gland
Infects B lymphoid cells (a latent state)
Infected B cells synthesize immunoglobulin
Mononucleosis is a polyclonal transformation of B cells
Autoantibodies are typical of the disease
Heterophile antibody that reacts with antigens on sheep erythrocytes
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Epstein – Barr virus(HHV-4)
30. Infectious mononucleosis
Like CMV, EBV is shed intermittently
Viruses are generated in pharynx and appears in saliva
It is a ‘kissing disease’
Mainly affects young adults
Incubation period is one month or more
fever, pharyngitis, enlargement of lymphnodes, spleen is palpable, liver
dysfunction with jaundice, transient macular rash
If ampicillin is given patient develop severe rash. Rarely CNS is involved
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31. Burkitt’s lymphoma
It is a highly malignant neoplasm occurs mainly in African children
The peak incidence is in 6-7 year old children
It presents as a tumour of jaw, orbit and other sites
If untreated, it is always fatal within a few months
It is responsive to early treatment with cyclophosphamide
EBV genome occur as circular episomal form in the tumour cells
Falciparum malaria is an important co-factor
Early AIDS patients can also develop BL
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32. Nasopharyngeal carcinoma (NPC)
It is a undifferentiated and invasive form nasopharyngeal cancer
It presents as enlarged cervical lymph node to which tumour has
metastasized
It is also associated with EBV
Here epithelial cells are involved
These tumours are inaccessible to surgery or chemotherapy
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33. B-cell lymphoma
Due to failure of T-cell control in immune compromised patients, are
liable to develop B-cell lymphomas associated with EBV
Oral hairy leucoplakia
a wart-like growth
white, roughened patches on buccal mucosa and sides of tongue
an epithelial focus of EBV replication
It is seen in male homosexuals who are HIV positive and transplant
patients
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34. Kaposi’s sarcoma-associated herpesvirus:
(KSHV) (HHV-8)
Kaposi’s sarcoma is a vascular tumours of mixed cellular
composition, of body cavity based lymphomas occurring in
AIDS patients
Main presentation is an indolent form
The lesions occur mainly on skin, lymphnodes and
gastrointestinal tract
It is more prevalent in male homosexuals
HHV-8 is also linked with multiple myeloma
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36. Properties
circular dsDNA
More than 100 types of HPV
Non-enveloped with icosahedral symmetry
Major & minor capsid protein comprises outer protein coat of the
virus
These viruses are difficult to grow invitro.
These viruses are highly tropic for epithelial cells of the skin and
mucous membranes.
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37. Three major regions comprise the HPV genome :
Early region (E1-E8) consists of genes responsible for transcription &
transformation
Late region codes for the major (L1) and minor (L2) capsid proteins
Control region contain the regulatory elements for transcription and
replication
Replication is in host cell nucleus
May undergo cell transformation
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39. Epidemiology and Diseases
• prevalence and diseases are type specific
• regional & ethnic variation in HPV types
• HPV 16,18,31 and 45
- in cervical cancers worldwide in order of prevalence
• HPV 16 & 18
- in 50% & 20% of all cases respectively
• HPV 16 and HPV 18
- in newborns
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40. Cont…
• Types 6 and 11
- genital warts (Condyloma acuminatum)
• Types 2,4,29 & 57
- in common skin warts
• Transmission
– Sexual contact
– Vertical transmission
– contact with infected urogenital secretions
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41. Laboratory Diagnosis
• Strong dependence of viral replication on the differentiated state of the host
cell
- difficulties in propagating papillomaviruses in vitro
• Pap smear (from Dr. Georgios Papanikolaou) conventional or liquid based
cytology (LBC)
• Molecular method
- hybridization technique to detect DNA in tissue blocks or exfoliated
cells
- tissue specimens, swabs, brushings and scrapes
cells for HPV DNA testing
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42. Influenza
Reading assignment
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• Type A = Hong Kong, Asian, Swine flu; Avian
Influenza (bird flu – emerging disease)
• Bird human (right now)
Pandemic: human human; antigenic shift
Influenza pandemic of killed 20+ million people!
(more than plague?)
The viruses of the last three global influenza
pandemics were first found in China.