Herpes Virus Flashcards
How common are herpes viruses
Infect most of the human population and people past middle age usually have antibodies of most herpes viruses except HHV-8
Name a few types of Herpes Virus
HSV-1 HSV-2 Varicella-Zoster Epstein-Barr CMV (cytomegalovirus)
What types of Herpes Virus are found in the alpha subfamily of herpes viruses and what diseases do they tend to cause
- HHV-1 - Herpes simplex type 1 = cold sores
- HHV-2 - Herpes simplex type 2 - genial herpes
- HHV-3 - Varicella-Zoster - chickenpox shingles
What diseases does HHV-4 virus cause (EBV)
Epstein-Barr Virus (EBV)
- Infectious mononucleosis/ glandular fever
- Burkitt’s lymphoma
What different structures are present in the Herpes virus
- Tegument
- Capsid
- Genome
- Lipid envelope
What is the tegument structure in the herpes virus
- The space between the envelope and capsid
- Contains virally encoded proteins and enzymes involved in the initiation of replication
What is a weakness about the lipid envelope of the herpes virus
Envelope is fragile and a damaged envelope is not infectious
What is the herpes virus sensitive to and why
- Drying
- Acids
- Detergents
- Organic solvents
As these will damage the envelope that will stop the virus from becoming infectious
Describe the replication process of herpes viruses
- Virus can bind to several host receptors that makes the envelope fuse with the plasma membrane
- Capsid moves to the nucleus and uses host polymerase to replicate
- Lytic infection - mRNA moves to cytoplasm, proteins built and assembled and the virus is exocytosed from the plasma membrane
What adaptation do herpes viruses have that allows them to carry out DNA synthesis in non-dividing cells
- Herpes viruses encode their own DNA-dependent DNA polymerase
- Some herpes viruses encode enzymes like thymidine kinase that allow the virus to grow in non-dividing cells that don’t contain precursors of DNA synthesis.
- Without this enzyme, neurotropic herpes viruses could not replicate because of the low amounts of certain DNA precursors in nerve cells
What is infection latency
- Infection remains for life
- Initial infection may be followed by latency with subsequent re-activation
Name some of the enzymes that the genome of HSV encodes for and what do they do
- DNA-dependent DNA polymerase
- Thymidine kinase (phosphorylates thymidine and other nucleotides)
- Ribonucleotide reductase (converts ribonucleotides to deoxyribonucleotide)
- Serine-protease (convert a scaffolding protein to its final form)
What are the surface proteins that are encoded by the HSV genome involved in
- Attachment
- Fusion of the viral membrane with that of the host cell
- Immune escape and other functions
How does HSV-1 tend to spread
Usually spread from mouth to mouth or by transfer of infectious virus to the hands after which the virus may enter the body via any wound or through the eyes
How does HSV-2 tend to spread
Frequently spread sexually - genital area, anus, rectum and upper alimentary tract
What is different about the way that HSV-1/2 affect humans compared to animals
HSV-1/2 infect many animals but only humans show symptoms
What cells do the HSV oral herpes viruses infect first
Epithelial mucosal cells or lymphocytes
Describe how latency occurs with HSV oral herpes viruses
- Virus travels up peripheral nerves to a nucleated neurone where it may stay for years followed by reactivation
- Oral Mucosa; trigeminal ganglia (e.g. primary herpetic gingivostomatitis)
- Genital mucosa; sacral ganglia
- No cytopathic effect in neurones as only immediate early proteins are made
Describe reactivation of the HSV oral herpes virus
- Virus travels down the nerve axon
- Lesions at the dermatome - reddened area gives rise to a macula and crusts to form a papula
What are the causes of reactivation
- Most triggers are stress-related e.g. UV, fever
- Factors causing some degree of immune suppression leading to renewal of virus proliferation in the nerve cell
- Recurrent infections are usually less pronounced than the primary infection and resolve more rapidly
What is the role of the innate immune response in herpes virus infection
- Interferon and natural killer cells are important in limiting the initial infection
What is the role of the humoral immunity in herpes virus infection
Antibodies against surface glycoproteins leads to neutralisation
What is the role of cellular immunity in herpes virus infection
- Cytotoxic T cells and macrophages
- The cell mediated and inflammatory response lead to some of the disease symptoms
How do you carry out the diagnosis of HSV infections
- Cells may be obtained from the base of the lesion (called a tank smear) and histochemistry performed
- Virus can be isolated from biopsy specimens, from lesions, where it forms cytopathic effects (plaque) including multinucleate cells
- Presence of HSV antibodies in patient diagnoses primary infection but recurrence is not usually accompanied by a rise in antibody levels
How do people contract Herpes Whitlow
When people come into contact with herpes infected body secretions, can be caused by either type of HSV and enter the body via small wounds on the hands or wrists
Can also be transferred by transfer of HSV-2 from genitals to the hands
How does herpes whitlow present
lesions/swelling in fingers/wrist
How does herpes gladiatorum spread
- Spreads by direct contact from skin lesions present in head and neck, often contracted by wrestlers
What herpes virus infects neonates and what does this infection result in
HSV-2 and the results are often fatal, but these infections are rare
How can neonates get HSV infection
If mother has active virus at the time of birth
If mother has active genital herpes at delivery a C-section is usually performed
Virus can be obtained in utero or on delivery
What are the symptoms of genital herpes
Primary infection is often asymptomatic but many painful lesions can develop
Urethra may be involved
Symptoms - fever, myalgia, glandular inflammation of the groin area
Secondary episodes = less severe and last shorter than first infection
What is HSV proctitis
Inflammation of the rectum and anus
What herpes virus causes HSV encephalitis usually
HSV-1
What happens in HSV encephalitis and what symptoms come with it
Febrile disease that may result in damage to one of the temporal lobes.
As a result there is blood in the spinal fluid and causes neurological symptoms like seizures
What herpes virus causes HSV meningitis
HSV-2
Who most frequently gets HSV meningitis and what symptoms are there
Male homos
Symptoms seem to resolve spontaneously
What kind of drugs are used for HSV chemotherapy and give example
Nucleoside Analog drugs e.g. acycloguanosine (acyclovir)
How do nucleoside analog drugs used in HSV chemo have high specificity
They take advantage of the drug activation via a viral enzyme - thymidine kinase
What is the benefit of high specificity drugs
They have few side effects
What is a drawback of nucleoside analog drugs
Resistant herpes mutants may show up but these are less virulent
AY BAWS CAN I HABE DE NOTE PLZ
The nucleoside analog drugs act against the replicating virus and are ineffective against latent virus
What do the herpes lesions contain
Infective virus
What is the characteristic rash that forms in Varicella-Zoster viruses
rash forms a belt around the thorax in many patients
What diseases does Varicella-Zoster virus cause
- Chicken-pox - usually childhood
- Shingles -
How is the highly infectious chickenpox spread
Respiratory aerosols or direct contact with skin lesions like with HSV, infection is via mucosa, but this time in the respiratory tract
What is the characteristic appearance of chickenpox
- Some of the sores are red spots and some are blisters
- The red spots will become blisters and new red spots will form
When does shingles present in a patient
This is the recurrence of varicella replication that usually occurs later in life
What are some characteristic presentations of shingles
- Severe pain in the nerve in which the latent infection has occurred
- Few days later chicken-pox like lesions occur but only in the immediately affected area - not widespread like the initial chicken pox infection
What are some complications that are related with chickenpox/shingles
- Pneumonia
- Fulminant encephalitis
- Cerebellar ataxia
- Traverse myelitis
- Guillian barre syndrome
- aseptic meningitis
What treatment options are there for chickenpox/shingles
- Acyclovir (or other nuceloside analogs) can be useful, especially in preventing dissemination in immunosuppressed patients
- Varicella immunoglobulin can also be used
- Normally only supportive care used in children who quickly recover if they mount an adequate cell-mediated response
- Vaccine
What are the common symptoms of EBV infection
- Fatigue
- Fever
- Inflamed throat
- Swollen lymph nodes in neck
- Enlarged spleen
- Swollen liver
- Rash
When do most infections of EBV occur
In childhood
What other symptoms can develop in early adult onset
- Glandular fever
- Swollen glands, tonsils, liver and spleen
- Infectious mononucleosis
What are some of the uncommon complications associated with EBV infection
- Further infections of other areas like brain, liver and lungs
- Severe anaemia
- Breathing difficulties from tonsils becoming swollen
- Ruptured spleen = surgery
What is EBV a causative agent of in Africa, the orient and the West respectively
EBV = causative agent of Burkitt’s lymphoma in Africa
EBV = causative agent of nasal pharyngeal carcinoma in the orient
EBV = causative agent of infectious mononucleosis in the west
What types of cells does EBV infect
- Cells must express receptor for complement C3d component
- Found on certain epithelial cells (oro- and naso-pharynx) and B lymphocytes
What is the difference in the interactions between B lymphocytes and epithelial cells
B cells - only semi-permissive for replicaiton of the virus - may be latent
Epithelial cells - allows complete lytic replication of the virus
What are the treatment options for EBV
- No drugs available to treat this
- This may reflect the absence of a thymidine kinase encoded by this virus
Describe the epidemiology of CMV (cytomegalovirus)
By 40, 50-80% of people are infected
Once virus enters body it stays for life
How is CMV (cytomegalovirus) spread
- In most secretions like saliva, urine, vaginal secretions and semen
- Can be spread to a foetus in a pregnant woman
Describe the life cycle of Cytomegalovirus (CMV) in the body
- Infects the upper respiratory tract and then local lymphocytes
- Circulating lymphocytes spread virus to other lymphocytes and monocytes in spleen and lymph nodes and then to epithelial cells
What symptoms are associated with CMV
Mostly harmless/asymptomatic
Some get fever, sore throat, fatigue and swollen glands
What complications are associated with CMV
- Can be serious if immunosuppressed: CMV retinitis in eye
- Congenital CMV infection can cause serious disease in children like hearing loss and developmental disabilities
- Post birth infections rarely have symptoms or complications
What treatment options are there for cytomegalovirus (CMV)
- No licensed drugs to treat congenital infection
- No vaccine available to prevent congenital infection but some vaccines are in development
