Herpesviridae Class Presentation for Virology discipline in Medicine by Sanskar Virmani, at School of Medicine, V. N. Karazin Kharkiv National University, Kharkiv, Ukraine.
Presentation is free to use for non-monetary purposes if the author (i.e., me) is properly cited and given due credits.
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2. Herpesviridae
Members of the herpesvirus family have been identified in
more than 80 different animal species
Eight have been identified as human pathogens
Herpes viruses are a leading cause of human viral disease,
second only to influenza and cold viruses
Herpes viruses infect most of the human population and
persons living past middle age usually have antibodies to
many of the human herpesviruses
Sanskar Virmani
5. After the primary infection, herpesviruses establish latency
in the infected host
Once a patient has become infected by herpes virus, the
infection remains for life
Intermittently, the latent genome can become activated, in
response to various stimulus, to produce infectious virions
Herpesviridae
Sanskar Virmani
6. Herpesviruses are classified into three groups based upon of
tissue tropism, pathogenicity and behavior
a herpesviruses
â˘Fast replicating
â˘Variable host range
â˘Typically destroy host cell
â˘Latency established in sensory ganglia
Herpes Simplex virus-1 and 2 (HSV-1 , HSV-2)
Varicella-Zoster virus (VZV)
Classification
Sanskar Virmani
7. b herpesviruses :
â˘Slowly replicating
â˘Restricted host range
â˘Infected cells enlarge (cytomegalia)
â˘Latency established in secretory glands, lymphoreticular
cells, kidneys
Cytomegalovirus (CMV)
Human Herpesvirus- 6 and 7 (HHV-6 , HHV-7)
Classification
Sanskar Virmani
8. g herpesviruses
â˘Replicate poorly
â˘Highly restricted host range
â˘Latency established in lymphoid tissue
(T-cell or B-cell specific)
Epstein-Barr Virus (EBV), a B-cell transforming virus
Human Herpesvirus-8 (HHV-8, KSHV)
Classification
Sanskar Virmani
9. Replication
ADSORPTION :
Envelope glycoproteins (e.g.- HSV proteins B and D) are
required for binding and penetration
Cellular receptors recognized by the herpesviruses are unknown
â˘EBV â C3d complement receptor
â˘CMV â Epidermal growth factor receptor
â˘HSV-1 âTumor necrosis factor receptor
Sanskar Virmani
10. PENETRATION
The nucleocapsid enters the cell by direct membrane fusion
with the cell plasma membrane
Capsids are transported to the nucleus
DNA passes into the nucleus, probably via nuclear pores
Herpesviridae - Replication
Sanskar Virmani
13. Virus Assembly
Assembly of the nucleocasid
occurs in the nucleus
The nucleocapsid âbudsâ through
intracellular membranes
ultimately taking up tegument
proteins beneath the envelope
Replication
Sanskar Virmani
16. The initial step of the interaction of virus with the cell is binding
to heparan sulfate, which is found on many cell types
Thus, almost any human cell type can be infected by HSV
In many cells, such as endothelial cells and fibroblasts,
infection is lytic
Neurons normally support a latent infection
If early and late proteins are made, the cell is set on a route to
lysis
Herpes Simplex Virus (HSV)
Sanskar Virmani
17. HSV-1 and HSV-2
first infect cells of the mucoepithelia , or enter through wounds
The site of the initial infection depends on the way in which the
patient acquires the virus
â˘HSV-1 above the waist
â˘HSV-2 below the waist
Herpes Simplex Virus (HSV)
Sanskar Virmani
18. The virus replicates in the epithelial
tissue yielding a characteristic âfever
blisterâ or âcold soreâ
The fluid in this blister is full of
infectious virus
The blister ulcerates and forms a
crusted lesion that heals without a
scar
HSV- Pathology
Sanskar Virmani
19. The virus replicates in the
epithelial tissue yielding a
characteristic âfever blisterâ or
âcold soreâ
The fluid in this blister is full of
infectious virus
The blister ulcerates and forms a
crusted lesion that heals without a
scar
HSV- Pathology
Sanskar
Virmani
20. Interferon and natural killer cells are important in limiting the
initial infection
Antibodies are directed against viral glycoproteins
The virus can also spread from one cell to another without
entering the extracellular space
This means that cell-mediated responses are vital in controlling
herpes infections; cytotoxic T cells and macrophages kill
infected cells
HSV- Pathology
Sanskar Virmani
21. HSV also infects neurons that innervate the epithelial tissue.
The virus travels along the neuron (retrograde transport)
â˘oral mucosa â trigeminal ganglia
â˘genital mucosa â sacral ganglia
HSV- Latency
A latent infection is established
in the nervous tissue
Sanskar
Virmani
22. HSV- Reactivation
Several agents may trigger recurrence
â˘stress
â˘exposure to strong sunlight
â˘fever
The virus can travels back down the nerve axon and arrives
at the mucosa that was initially infected
Vesicles containing infectious virus are formed on the
muscosa and the virus spreads
Recurrent infections are usually less confirmed than the
primary infection and resolve more rapidly
Sanskar
Virmani
23. HSV Infections
Oral Herpes
Both HSV-1 and HSV-2
Genital Herpes
Primarily HSV-2 (but 10% cases HSV-1)
Involve a transient viremia (fever, myalgia, glandular
inflammation in the groin area)
Secondary infections are frequently less severe
Herpes Keratitis
An infection of the eye
Primarily HSV-1
Sometimes recurrent
Leading cause of corneal blindness in the US
Sanskar
Virmani
24. Herpes gladiatorum
Contracted by wrestlers
Spreads by direct contact from skin lesions
Usually appears in the head and neck region
Also seen in other contact sports such as rugby
(Herpes Rugbeiorum )
HSV Encephalitis
Typically HSV-1
Most common cause of sporadic viral encephalitis
Relatively rare (1000 cases/yr)
HSV Infections
Sanskar Virmani
25. Varicella-Zoster Virus (VZV)
Initial infection usually in childhood with Varicella virus (HHV-3)
â Chicken Pox
It is spread by respiratory aerosols or direct contact with lesions
The virus establishes latency within the dorsal root ganglia
Years or decades later, the virus (Herpes zoster) may
reactivate â Shingles
Sanskar Virmani
26. Zoster means girdle, from the characteristic rash that forms a
belt around the thorax
Varicella-Zoster Virus (VZV)
Rash along dermatomes
Sanskar Virmani
27. Trigeminal nerve reactivation
â˘uveitis, keratitis, conjunctivitis
Cranial nerve reactivation
â˘Bells palsy: a condition that causes the facial muscles to
weaken or become paralyzed. It's caused by trauma to
the 7th cranial nerve and is not permanent.
â˘Ramsay-Hunt syndrome: virus spread to facial nerves.
Characterized by intense ear pain, a rash around the ear,
mouth, face, neck, and scalp, and paralysis of facial
nerves. Symptoms may include hearing loss, vertigo,
and tinnitus.
VZV- Pathology
Sanskar Virmani
28. VZV- Pathology
Post-herpetic neuralgia: chronic burning or itching pain;
hyperesthesia (increased sensitivity to touch)
Acyclovir, valacyclovir, and famciclovir are approved for the
treatment of VZV
Sanskar Virmani
29. ďą EBV (HHV-4) is responsible for infectious mononucleosis
ďą The primary infection is often asymptomatic, but the patient may shed
infectious virus for many years
ďą Some patients develop symptoms after 1-2 months
â˘malaise
â˘lymphadenopathy
â˘tonsillitis
â˘enlarged spleen and liver
â˘fever
â˘occasional rash
ďą The severity of disease often depends on age, but usually resolves in 1
to 4 weeks
ďą EBV may be transmitted by blood transfusion
Epstein Barr Virus (EBV)
Sanskar Virmani
30. The virus uses the C3d complement receptor for entry and
thus infects only a small number of cell types
â˘oro- and naso-pharynx
â˘B lymphocytes
Lytic Infection
The ZEBRA protein is expressed in epithelial cells
This transcription factor promotes the expression of early
genes -> active virus replication and lytic infection
Epstein Barr Virus (EBV)
Sanskar Virmani
31. Latency
B lymphocytes are only semi-permissive for replication and EBV
infection is often latent
The infected B-lymphocyte contains a few episomes
Only a few genes are expressed from the episome, including two
membrane proteins that are oncogenic
â˘Burkitts lymphoma
â˘nasal pharyngeal carcinoma
In addition:
â˘infectious mononucleosis
â˘chronic fatigue syndrome
Epstein Barr Virus (EBV)
Sanskar Virmani
32. Cytomegalovirus (CMV)
CMV (HHV-5) derives its name from the fact that it can form multinucleated
cells (syncytia)
Some cells such as macrophages and fibroblasts support a productive
infection
Other cells such as T lymphocytes and stromal cells of the bone marrow set
up latent infection
The virus is spread via most secretions, particularly saliva, urine, vaginal
secretions and semen
CMV may also be spread by blood transfusion and organ transplant
CMV causes no symptoms in children and mild disease in adults
Sanskar Virmani
33. The virus elicits both humoral and cell-mediated immunity but
the infection is not cleared
The virus may reactivate, particularly in cases of
immunosuppression
â˘Organ transplant patients
â˘Immunosuppressive disease
(CMV-retinitis occurs in up to 15%
of all AIDS patients; also pneumonia,
colitis, esophagitis and encephalitis)
Gancyclovir may be used, especially to
treat retinitis in the immunosuppressed
CMV
HO
HN
N
N
O
H2N N
O
OH
Sanskar Virmani
34. Human Herpesvirus 8 (HHV-8) , or Kaposi Sarcoma Herpes
Virus (KSHV), is associated with the development of Kaposiâs
Sarcoma in AIDS patients.
Kaposi's sarcoma is a type of cancer
that affects men and is
rarely seen in women.
Although KS mainly affects the skin,
the mouth, and the lymph
nodes, it can also involve
the bowels and lungs.
HHV 8 is sexually transmitted.
Human Herpesvirus 8
Sanskar
Virmani
35. Thank You
Sanskar Virmani, MM-206 (2022-2023)
School of Medicine, V. N. Karazin Kharkiv National University