viral infections Flashcards
Describe the key characteristics of viruses
- 20 nm - 1 um in size
- RNA or DNA
- No independent metabolism and no organelles
- Simple protein coat (and cell membrane from host cell)
Describe viral structure
Describe influenza structure
- Contain either RNA or DNA genome surrounded by protective viral encoded protein coat = capsid
- complete viral particle = virion
- main function of virion is to deliver its DNA/RNA genome into host cell to allow fenome to be expressed
- viral genome often associated within protein capsid formed of nucleoproteins, forms nucleocapsid
- in enveloped viruses nucleocapsid is surrounded by a lipid bilayer/ envelope derived from modified host cell membrane, studded with outer layer of virus envelope glycoproteins
- viral capsids function as a shell to protect viral genome from nucleases, and during infection attaches virion to specific receptors exposted on prospective host cell
- Influenza virus structure shown:
- influenza virion spherical in shape
- enveloped virus with lipid membrane taken from host cell
- inserted into the membrane are glycoplipids, called H spike or N spike as they are proteins linked to sugars – known as HA (hemagglutinin) and NA (neuraminidase), used to subtype influenza e.g. H1N1
What is the baltimore classification of viruses?
How many classes are there, describe each class (don’t worry too much about this)
- Baltimore classification of viruses is a classification system that groups viruses into families depending on their type of genome (DNA/ RNA, single stranded (ss), double stranded (ds) and their method of replication.
- 7 groups:
- 1 –> dsDNA viruses –> must enter host nucleus before replication, require host cell polymerases and host cell to be in S phase of cell cycle
- Examples: adenoviruses, herpesviruses, papillomaviridae
- 2–> ssDNA viruses –> most have circular genomes, form dsDNA in host nucleus.
- group 3 –> dsRNA virus –> replicates within host cytoplasm
- 4 and 5 –> singlge stranded RNA viruses –> replication happens in cytoplasm or nucleus
- group 4 –> positive sense RNA viruses, can be directly accessed by host ribosomes to immediately form proteins, reproduce in cytoplasm
- group 5–> negative sense RNA viruses, cannot be directly accessed by host ribosomes, need to be transcribed by viral polymerase into a “readable” form.
- Group 6 –> positive sense single stranded RNA viruses that replicate through DNA intermediate (retroviruses, use reverse transcriptaase to convert +ve sense RNA into DNA, then transcribed into RNA, spliced by integrase, then tranlsated into viral protein.
- Group 7 –> double stranded DNA virus that replicates through single stranded RNA intermediate (e.g. Hep B). Double stranded DNA genome serves as template for production of viral mRNA which then serves as template for viral reverse transcriptase.
- 1 –> dsDNA viruses –> must enter host nucleus before replication, require host cell polymerases and host cell to be in S phase of cell cycle
Describe the viral lifecycle
- Viruses follow several stages to infect host cells: attachment, penetration, uncoating, biosynthesis, maturation, and release.
- after binding host receptors using viral proteins, animal viruses enter through endocytosis or membrane fusion (penetration)
- many viruses are host specific and only infect a certain type of host cell within certain tissues
- once virus has penetrated host cell it becomes uncoated, releasing viral contents.
- during biosynthesis viral replication depends on the class of virus.
- ssDNA, host enzymes will synthesise a second strand complementary to genome strand, producing dsDNA. dsDNA now replicated, transcibed and translated.
- if viral genome RNA: +ssRNA can be translated directly to make viral proteins, it acts like cellular mRNA. If -ssRNA, it must be replicated into +ssRNA by viral RNA dependent RNA polymerase, brought in by the virus.
- alternative mechanism for +ssRNA viruses is that they carry reverse transcriptase within the capsid, synthesises complementary ssDNA, which is then made into dsDNA which integrates into the host genome. Intergrated viral genome = provirus and can remain in host to establish chronic infection.
- Once viral replication has occured, assembly of new virions occurs. Viral genome, enclosed within the capsid.
- Then release, viral particles are released, and can become enveloped in host cell lipid membrane, or become covered by viral envelope protein.
What allows viruses to be specific in the cell type that they infect?
- Specificity of the cells viruses infect is encoded by the types of proteins they express within the viral coat and the receptors expressed on the host cell
Define:
Acute infection
Latent infection
Chronic/ persistent infection
- Acute infection = primary infection usually followed by clearance and immunity
- Latent infection = primary infection followed by restricted viral gene expression (very little detectable virus, can be later reactivated e.g. chicken pox and shingles; reactivated as you get older, immunosuppressed or stressed)
- Chronic/ persistent infection = primary infection followed by persistent viral replication, continues to cause some damage
Describe viral pathogenesis
Access –> e.g. contact, respiratory, ingestion
Adherence –> express viral proteins
Invasion –> normally by binding to certain surface molecule, triggers endocytosis/ membrane fusion
Multiplication –> hijack cellular machinery
Evasion –> intracellular prevents detection
Resistance –> viruses evolve rapidly, often produce many errors which enable evolution into more effective virus, therefore good at resisting antimicrobial tx.
Damage –> damage to host cells either directly or indirectly
Transmission –> respiratory droplets, diarrhoea etc…
Give some common viral infections that cause the common cold
Rhinoviruses
Parainfluenza virus
Respiratory syncytial virus
Give some viral causes of encephalitis/ meningitis / myelitis
Encephalitis/ meningitis:
- Measles
- Arbovirus
- Rabies
- JC virus
- LCM virus (lymphcytic choriomeningitis)
myelitis:
Poliovirus
HTLV-1 (human T cell leukaemia virus)
Give some viral causes of skin infection
Varicella/herpes zoster virus
Human herpesvirus 6
Human papillomavirus
Smallpox
Rubella
measles
Coxsackie A virus
Common viral cuases of pneumonia?
Influenza virus A/B
parainfluenza
RSV
Adenovirus
SARS coronavirus
Give common viral causes of gastroenteritis
adenovirus
rotavirus
norovirus
astrovirus
coronavirus
Give common viral causes of STI
herpes simplex type 2
human papillomavirus
HIV
viral cause of parotitis?
mumps
viral cause of eye infection?
herpes simplex virus
adenovirus
cytomegalovirus
viral cause of gingivostomatitis
herpes simplex type 1
causes of cardiovascular and pancreatic infection?
coxsackie B virus
what techniques are involved in the microbiological diagnosis of viral infection?
What are their uses?
Microscopy and culture no longer used in diagnosis
Serology (Ab detection) is widely used:
- negative in the early stages of infection
- sometimes difficult to interpret (have to look at IgM and IgG molecules, need two samples, often a week apart, expect to see rising AB level).
- positive in chronic, latent and past infection
PCR tests from swabs/ blood samples/ other body fluids:
- positive in early stages of acute infection
- highly sensitive and specific tests (for acute and chronic infections)
- negative in latent and past infection
- can identify antiviral resistance genes
Antigen detection tests occasionally used, antigen = protein on viral coat.
Immunohistochemistry staining of tissues may also be possible with biopsied tissue.
What are the viral infections with skin manifestations?
- EBV –> Epstein barr virus
- CMV –> cytomegalovirus
What is the infection shown?
What type of infection is it, where does it enter the body
Where does it tend to manifest?
Who does it tend to affect?
Is there a specific diagnostic test or tx for this?
hand, foot and mouth disease
Enterovirus that enters via the gut, manifests within the skin
Produces lesions on the skin and ulcers on the mouth
No diagnostic tests for this virus, relies on clinical experience.
Commonly affects children, once theyve got the infection it will pass and they wont be affected again.
What pathology is shown?
Measles with characteristic rash; initial sx of measles develop around 10 days after infection. Infection normally clears in 7-10 days.
Initial Sx include: cold like sx (runny nose, sneezing and cough), sore red eyes that may be sensitive to light, high temperature (fever), koplik spots on the inside of the cheeks.
Koplik spots = often manifest 2-3 days before measles rash itself, white lesions in buccal mucosa (charactersitic feature of measles).
A few days later red- brown blotchy rash appears, usually starting on head/ upper neck before spreading outwards to the rest of the body.
HPV –> how common is it?
What can it cause?
What areas does it affect?
What cancers are linked to HPV?
HPV virus –> very common group of viruses, can cause genital warts, warts of the skin or lead to cancer through abnormal changes to infected cells. There are over 100 types. Many types of HPV affect the mouth, throat or genital area.
example within the skin: veruca strain is benign, often the immune system able to deal with it itself.
Type that causes genital warts and cervical subtype. Precursor for cervical cancer, hence why screening looks for HPV virus.
Acetic acid staining is used to detect the virus on the cervix.
Cancers linked to HPV include: cervical, anal, penile, vulval, vaginal, some types of head and neck cancer.
HSV:
what types are there
where does it normally infect
what can it cause?
where can it sit latent?
what cranial nerve can be affected?
- Herpes simplex virus ( HSV1 and HSV2)
- usually infects perioral and genital areas —> localised painful vesicles
- Can also cause HSV encephalitis
- May become latent in dorsal root ganglia –> recurrence
- Can also recur in the facial nerve –> bell’s palsy
VSV:
What does it stand for?
where does it commonly infect?
what can it cause?
where can it remain latent? what is reinfection called?
what specific nerve can it affect?
- Varicella zoster virus (chickenpox virus) –> normally causes fever and vesicles distributed across the trunk
- in centripetal distribution
- Can also cause VZV meningitis
- Can become latent in dorsal root ganglia –> recurrence (zoster/ shingles), tends to follow a specific nerve distribution
- Can also recur in facial nerve = ramsey hunt syndrome
Which cranial nerve can be affected by herpes zoster virus?
remember varicella zoster = primary infection, chickenpox
herpes zoster is reactivation of latent VSV within the dorsal root ganglia.
It can sit dormant within the trigeminal nerve and become recativated.
When it reactivates it causes vesicular lesions, can cause lesions across all three distributions of the trigeminal nerve –> if this occurs within the opthalmic division this can be very serious.
What is ramsay hunt syndrome?
Ramsay hunt syndrome = reactivation of VZV within the facial nerve causing hemiparalysis of the facial muscles
infection gives rise to vesiculation and ulceration of the external ear and ipsilateral anterior two thirds of the tongue and soft palate, as well as ipsilateral facial neuropathy (in CN VII), radiculoneuropathy, or geniculate ganglionopathy.
What is EBV?
What family of viruses does it comes from?
what does it cause?
how is it transmitted?
what cells does it infect?
who tends to become infected?
what are the symptoms?
how is it diagnosed?
what are you at increased risk of after infection?
- from the human herpes virus family (1 0f 8) = HHV-4
- Causes “glandular fever” or “infectious mononucleosis”
- Transmitted by both oral and genital secretions
- Infects B lymphocytes and develops into a latent infection
- Infection occurs in 50% of children by age 5 and 90% of adults
- Sx of infection are more severe with increasing age:
- fever
- pharyngitis
- lymphadenopathy
- splenomegly
- hepatitis
- Diagnosed by:
- GFST (glandular fever screening test, non specific but cheap and easy).
- blood films –> B lymphocytes replicate massively
- serology and PCR tests
- immunohistochemistry –> AB targeted at EBV
- Reactivation occurs at random and is usually asymptomatic
- EBV is associated with certain cancers (lymphoma, nasopharyngeal) and MS
What is CMV?
What family of viruses is it from?
what does it cause in: most people, adolescents, weakened immune system, pregnancy, newborn
how is it transmitted?
what cell types does it infect?
who is often affected by infection?
- CMV = cytomegalovirus
- from human herpes virus family )1 of 8) = HHV-5
- Causes a type of glandular fever or infectious mononucleosis in young adults but most people with CMV infection have no symptoms- a few infected people feel ill and have fever.
- In young adults have symptoms of infectious mononucleosis- fever, fatigue, lymphadenopathy, BUT NO pharyngitis (only with EBV)
- In those with weakened immune system CMV infection can be severe –> e.g. AIDS can cause CMV retinitis (blindness), encephalitis , pneumonia and ulcers within the intestine or oesophagus.
- In pregnacy –> highly dangerous can lead to miscarriage, still birth and death of newborn.
- in newborn can cause extensive damage to liver and brain, learing loss, intellectual disability.
- transmitted by oral and genital secretions, urine, blood, breast milk and congenital (from mother to child)
- infects multiple cell types and develops into a latent infection
- infection has occurred in around 50% of adults
CMV:
what are the sx and how do they change with age?
What does congenital infection cause?
- CMV sx –> often asymptomatic
- In young adults –> infectious mononucleosis type symptoms –> fever/ fatigue/ lymphadenopathy (no pharyngitis)
- in immunosuppressed –> severe infection, encephalitis, lesions in intestines/ oesophagus, retinitis (blindness), pneumonia, fever.
- In pregnancy –> can lead to miscarriage, infant death
- Congential infection causes hearing loss, visual loss, seizures, microcephaly.
- In immunocompetent people infection usually self limiting.
CMV:
how is it diagnosed?
what can cause reactivation?
what can reactivation cause?
- Diagnosed by: blood film, serology, PCR, immunohistochemistry
- Reactivation occurs at random or when immunocompromised
- CMV in severe cases –> causes retinitis, pneumonia, hepatitis and colitis –> subtle different presentation that bacterial infection
- CMV reactivation in healthy people–> fatigue, fever, sore throat, headache, muscle aches, lymphadenopathy
