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Herpesviridae
BY
SANSKAR VIRMANI
MM-206 (2022-2023)
SCHOOL OF MEDICINE, V. N. KARAZIN KHARKIV
NATIONAL UNIVERSITY
Sanskar Virmani
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
Herpesviridae
The Herpesviridae family comprises large,
DNA-containing enveloped viruses
Sanskar Virmani
glycoprotein B (gpB) spikes
visible in membrane
Herpesviridae
Sanskar
Virmani
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
Herpesviruses are classified into three groups based upon of
tissue tropism, pathogenicity and behavior
a herpesviruses
•Fast replicating
•Variable host range
•Typically destroy host cell
•Latency established in sensory ganglia
Herpes Simplex virus-1 and 2 (HSV-1 , HSV-2)
Varicella-Zoster virus (VZV)
Classification
Sanskar Virmani
b herpesviruses :
•Slowly replicating
•Restricted host range
•Infected cells enlarge (cytomegalia)
•Latency established in secretory glands, lymphoreticular
cells, kidneys
Cytomegalovirus (CMV)
Human Herpesvirus- 6 and 7 (HHV-6 , HHV-7)
Classification
Sanskar Virmani
g herpesviruses
•Replicate poorly
•Highly restricted host range
•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
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
•EBV → C3d complement receptor
•CMV → Epidermal growth factor receptor
•HSV-1 →Tumor necrosis factor receptor
Sanskar Virmani
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
Adsorption
and
Penetration
Herpesviridae - Replication
Sanskar
Virmani
Replication
Herpesvirus replication is a carefully regulated, multi-step process
Sanskar
Virmani
Virus Assembly
Assembly of the nucleocasid
occurs in the nucleus
The nucleocapsid “buds” through
intracellular membranes
ultimately taking up tegument
proteins beneath the envelope
Replication
Sanskar Virmani
Sanskar Virmani
Infection and Disease
Designation
Common
Name
Subfamily Associated Diseases
HHV-1 HSV-1 Alpha Oral Herpes (cold sore), Genital Herpes
HHV-2 HSV-2 Alpha Genital Herpes
HHV-3 VZV Alpha Chicken Pox, Shingles
HHV-4 EBV Gamma Mononucleosis, Lymphoma, Carcinoma
HHV-5 CMV Beta Mononucleosis, Retinitis, Transplant Rejection
HHV-6 HHV-6 Beta Roseola infantum, Mononucleosis syndrome,
Chronic fatigue syndrome, Multiple Sclerosis
HHV-7 HHV-7 Beta Roseola infantum, Mononucleosis syndrome
HHV-8 KSHV Gamma Kaposi’s Sarcoma
Sanskar
Virmani
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
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
•HSV-1 above the waist
•HSV-2 below the waist
Herpes Simplex Virus (HSV)
Sanskar Virmani
The virus replicates in the epithelial
tissue yielding a characteristic “fever
blister” or “cold sore”
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
The virus replicates in the
epithelial tissue yielding a
characteristic “fever blister” or
“cold sore”
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
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
HSV also infects neurons that innervate the epithelial tissue.
The virus travels along the neuron (retrograde transport)
•oral mucosa → trigeminal ganglia
•genital mucosa → sacral ganglia
HSV- Latency
A latent infection is established
in the nervous tissue
Sanskar
Virmani
HSV- Reactivation
Several agents may trigger recurrence
•stress
•exposure to strong sunlight
•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
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
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
Varicella-Zoster Virus (VZV)
Initial infection usually in childhood with Varicella virus (HHV-3)
→ 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 → Shingles
Sanskar Virmani
Zoster means girdle, from the characteristic rash that forms a
belt around the thorax
Varicella-Zoster Virus (VZV)
Rash along dermatomes
Sanskar Virmani
Trigeminal nerve reactivation
•uveitis, keratitis, conjunctivitis
Cranial nerve reactivation
•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.
•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
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
 EBV (HHV-4) is responsible for infectious mononucleosis
 The primary infection is often asymptomatic, but the patient may shed
infectious virus for many years
 Some patients develop symptoms after 1-2 months
•malaise
•lymphadenopathy
•tonsillitis
•enlarged spleen and liver
•fever
•occasional rash
 The severity of disease often depends on age, but usually resolves in 1
to 4 weeks
 EBV may be transmitted by blood transfusion
Epstein Barr Virus (EBV)
Sanskar Virmani
The virus uses the C3d complement receptor for entry and
thus infects only a small number of cell types
•oro- and naso-pharynx
•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
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
•Burkitts lymphoma
•nasal pharyngeal carcinoma
In addition:
•infectious mononucleosis
•chronic fatigue syndrome
Epstein Barr Virus (EBV)
Sanskar Virmani
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
The virus elicits both humoral and cell-mediated immunity but
the infection is not cleared
The virus may reactivate, particularly in cases of
immunosuppression
•Organ transplant patients
•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
Human Herpesvirus 8 (HHV-8) , or Kaposi Sarcoma Herpes
Virus (KSHV), is associated with the development of Kaposi’s
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
Thank You
Sanskar Virmani, MM-206 (2022-2023)
School of Medicine, V. N. Karazin Kharkiv National University

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Herpesviridae Presentation

  • 1. Herpesviridae BY SANSKAR VIRMANI MM-206 (2022-2023) SCHOOL OF MEDICINE, V. N. KARAZIN KHARKIV NATIONAL UNIVERSITY Sanskar Virmani
  • 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
  • 3. Herpesviridae The Herpesviridae family comprises large, DNA-containing enveloped viruses Sanskar Virmani
  • 4. glycoprotein B (gpB) spikes visible in membrane Herpesviridae 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 •Fast replicating •Variable host range •Typically destroy host cell •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 : •Slowly replicating •Restricted host range •Infected cells enlarge (cytomegalia) •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 •Replicate poorly •Highly restricted host range •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 •EBV → C3d complement receptor •CMV → Epidermal growth factor receptor •HSV-1 →Tumor 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
  • 12. Replication Herpesvirus replication is a carefully regulated, multi-step process Sanskar Virmani
  • 13. Virus Assembly Assembly of the nucleocasid occurs in the nucleus The nucleocapsid “buds” through intracellular membranes ultimately taking up tegument proteins beneath the envelope Replication Sanskar Virmani
  • 15. Infection and Disease Designation Common Name Subfamily Associated Diseases HHV-1 HSV-1 Alpha Oral Herpes (cold sore), Genital Herpes HHV-2 HSV-2 Alpha Genital Herpes HHV-3 VZV Alpha Chicken Pox, Shingles HHV-4 EBV Gamma Mononucleosis, Lymphoma, Carcinoma HHV-5 CMV Beta Mononucleosis, Retinitis, Transplant Rejection HHV-6 HHV-6 Beta Roseola infantum, Mononucleosis syndrome, Chronic fatigue syndrome, Multiple Sclerosis HHV-7 HHV-7 Beta Roseola infantum, Mononucleosis syndrome HHV-8 KSHV Gamma Kaposi’s Sarcoma 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 •HSV-1 above the waist •HSV-2 below the waist Herpes Simplex Virus (HSV) Sanskar Virmani
  • 18. The virus replicates in the epithelial tissue yielding a characteristic “fever blister” or “cold sore” 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 “fever blister” or “cold sore” 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) •oral mucosa → trigeminal ganglia •genital mucosa → sacral ganglia HSV- Latency A latent infection is established in the nervous tissue Sanskar Virmani
  • 22. HSV- Reactivation Several agents may trigger recurrence •stress •exposure to strong sunlight •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) → 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 → 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 •uveitis, keratitis, conjunctivitis Cranial nerve reactivation •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. •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.  EBV (HHV-4) is responsible for infectious mononucleosis  The primary infection is often asymptomatic, but the patient may shed infectious virus for many years  Some patients develop symptoms after 1-2 months •malaise •lymphadenopathy •tonsillitis •enlarged spleen and liver •fever •occasional rash  The severity of disease often depends on age, but usually resolves in 1 to 4 weeks  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 •oro- and naso-pharynx •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 •Burkitts lymphoma •nasal pharyngeal carcinoma In addition: •infectious mononucleosis •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 •Organ transplant patients •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 Kaposi’s 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