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.

1. MEDICAL VIROLOGY
Virology for PC-II 1

2. 2
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?

3. Clinically-important viruses (just a few examples!)
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HepC

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

5. Virology for PC-II 5

6. Virology for PC-II 6

7. Medical Important DNA Viruses
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8. Herpesviridae
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Herpes virus

9.  Family -- important human
pathogens
 Lifelong persistent infections
 Periodic reactivation
 Latency is a special property
 Replication: Nuclear.
 Assembly: Nuclear.
Morphology
 Spherical -- 150-200nm
 Cubic symmetry
 Possess ds DNA
 Enveloped
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Herpes virus

10. Herpes virus types that infect humans
 Herpes simplex 1 & 2: (cold sores, genital herpes)
 Varicella zoster : (chicken pox, shingles)
 Cytomegalovirus (infectious mononucleosis)
 Epstein-Barr virus (mononucleosis, Burkitt’s lymphoma)
 Human herpesvirus 6 & 7 (Roseola)
 Human herpesvirus 8 (Kaposi’s sarcoma)
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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
DNA Viruses for PC -II 12
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
DNA Viruses for PC -II 13

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
DNA Viruses for PC -II 14

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
DNA Viruses for PC -II 16

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
DNA Viruses for PC -II 17

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
DNA Viruses for PC -II 19

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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DNA Viruses for PC -II

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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DNA Viruses for PC -II

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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DNA Viruses for PC -II
Varicella-Zoster virus

24. Zoster in AIDS patient
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DNA Viruses for PC -II

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
DNA Viruses for PC -II 27

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
DNA Viruses for PC -II 31

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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35. Human Papillomaviruses (HPV)
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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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DNA Viruses for PC -II

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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DNA Viruses for PC -II

38. Papillomavirus pathogenesis
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DNA Viruses for PC -II

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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DNA Viruses for PC -II

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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DNA Viruses for PC -II

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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DNA Viruses for PC -II

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.

43. Any questions ???