Midterm IV (Leiel) Flashcards
Classification of viruses by morphology
- Helical shape: helical array of capsid proteins (capsomeres) around a helical filament of nucleic acid (DNA or RNA).
- Icosahedral shape (most common): near spherical, requires a minimum of 12 capsomeres. Capsomeres can be pentons (curved, surrounded by five other capsomeres) or hexons (flat, surrounded by six), these may be of the same or different protein subunits.
- Prolate shape: elongated icosahedron (e.g.: head of bacteriophages), cylinder shaped with cap at either end.
- Envelope: nucleocapsid is surrounded by a modified form of a cellular membrane (glycoproteins and membrane from infected cell), important for infectivity but makes the virus more labile to environmental factors (e.g.: pH, heat) than the stable naked viruses (only protein coating).
- Complex: capsid is neither purely helical nor icosahedral.
Culture on monolayer tissue
A layer of cells in which no cell is growing on top of another, but all are growing side by side and often touching each other on the same growth surface.
To produce a monolayer:
- Mince the meat
- Add trypsin (cell-to-cell contact is inhibited)
- Plate to produce a monolayer
Monolayer culture helps to detect cytopathogenic effects of viruses.
HHV-1
HHV-1 is also known as HSV-1 (Herpes Simplex virus 1)
This is an enveloped virus, double stranded linear DNA virus, it is able to establish lifelong persistent infections and undergo periodic activation.
It creates intranuclear inclusion bodies (Cowdry bodies).
HSV-1 is usually associated with infections above the waist, spreads usually by droplets, and usually limited to the oropharynx, causing herpes labialis.
Infection:
The virus replicates at the site of the infection → local nerve ending invasion → retrograde axonal flow to dorsal root ganglia → latency (non-replicating state)
It remains latent in the trigeminal ganglia, and with a proper provocative stimuli→ reactivation.
Diseases:
- Gingivostomatitis
- Herpes encephalitis: lesions are limited to one of the temporal lobes; it gives rise to erythrocytes in the CSF.
- Herpetic keratitis: limited to one eye, permanent scarring, corneal damage, blindness.
- Herpetic whitlow: infection of the finger (in thumb-sucking children, nurses, dentists, people who have genital HSV infections).
- Eczema herpeticum: acquired by children with active eczema.
Transmission: vertical transmission (TORCH)
In vesicle fluid, saliva, vaginal secretions (mixing and matching of mucous membranes= MMMM).
Diagnosis:
Scraping of the base of a lesion, biopsy, cultivation (HeLa, rabbit kidney cells), PCR.
Therapy:
Acyclovir, valcyclovir, famcyclovir (nucleoside analogue).
HHV-2
HHV-2 is also known as HSV-2 (Herpes Simplex virus 2)
This is an enveloped virus, double stranded linear DNA virus, it is able to establish lifelong persistent infections and undergo periodic activation.
It creates intranuclear inclusion bodies (Cowdry bodies).
HSV-2 is usually associated with infections below the waist, causes viremia and associated systemic influenza-like symptoms. Usually genital routes→ herpes genitalis.
Infection:
The virus replicates at the site of the infection → local nerve ending invasion → retrograde axonal flow to dorsal root ganglia → latency (non-replicating state)
It remains latent in the sacral ganglia, and with a proper provocative stimuli→ reactivation.
Diseases:
- HSV meningitis
- Neonatal herpes: HSV-2 acquired in utero or in the birth canal, prevention by caesarean section.
- Painful inguinal lymphadenopathy
Transmission: vertical transmission (TORCH)
- In vesicle fluid, saliva, vaginal secretions (mixing and matching of mucous membranes= MMMM).
Diagnosis:
Scraping of the base of a lesion, biopsy, cultivation (HeLa, rabbit kidney cells), PCR.
Therapy:
Acyclovir, valcyclovir, famcyclovir (nucleoside analogue).
CMV
DNA virus that can be isolated from urine, blood, throat swab, saliva, tears, breast milk, semen, stool, vaginal secretion.
Like other viruses from herpes virus family- the virus remains latent. It is found in mononuclear leukocytes (B and T cells, macrophages), and reactivates in immunosuppression.
Transmission:
Congenital, oral and sexual route, blood transfusion and tissue transplantation (TORCH infection).
Diseases:
- Congenital infection:
- Rash, microcephaly, ventriculomegaly, hearing loss, hepatosplenomegaly and jaundice, intracerebral calcifications, mental retardation, seizures. Can also cause hydrops fetalis.
- In normal immune system: mononucleosis-like syndrome (Monospot test is negative).
- In immunodeficiency: CMV retinitis, CMV colitis with ulcerated walls, linear ulcerations in esophagus (esophagitis), pneumonia.
Diagnosis:
- Owl’s eye inclusion bodies, ELISA, tube agglutination.
- Titers of CMV-specific IgM antibody (very high in AIDS patients)
Therapy:
Ganciclovir
Foscarnet (phosphonoformic acid) used when Resistance to ganciclovir is acquired by mutation in UL97 gene.
Describe Paul Bunnell test
Paul-Bunnell test: hemagglutination by antibodies produced against EBV
This is a heterophile antibody test: specific for heterophile antibodies produced by the immune system in response to EBV infection.
Heterophile means it reacts with proteins across species lines. It can also mean that it is an antibody that reacts with antigens other than the antigen that stimulated it (an antibody that crossreacts).
Classification of viruses by nucleic acids
Classification according to the Baltimore Classification of viruses:
- dsDNA (e.g. Herpes simplex virus)
- ssDNA (parvovirus)
- dsRNA (e.g. reovirus)
- +ssRNA (e.g. Enterovirus)
- –ssRNA (e.g. Influenza A virus)
- ssRNA (Retrovirus)
- Nicked dsDNA (e.g. Hepatitis B virus)
Cultivation of viruses in the lab
Cultivation is in embryonated egg, or monolayer cell tissue.
Culture media:
- Liquid or semi liquid
- Components: serum, nutrients (amino acids and carbohydrates), vitamins, growth factors, antibiotics and an indicator.
- Sterilization by filtering to avoid contamination (which can be by mycoplasma or other bacteria, fungi or endogenous viral infections).
EBV (Epstein-Barr virus)
Double-stranded DNA virus, primarily transmitted through saliva.
Target cell: B lymphocytes → continuous cell lines can be established (remains latent in B cells). EBV envelope glycoprotein binds CD21 to infect B cells.
Reactive cytotoxic CD8+ T cells (Downey or atypical cells) are seen on blood smear.
EBV is screened together with CMV because the symptoms are similar.
Diseases:
-
Mononucleosis: fever, malaise, lymphadenopathy, hepatosplenomegaly (due to proliferation of T cells), fatigue, pharyngitis and tonsillar exudates.
- Complication: rupture of the spleen, meningoencephalitis.
- EBV-induced lymphoproliferative diseases: people lacking T-cell immunity suffer from life-threatening polyclonal leukemia-like B-cell proliferative diseases and lymphoma.
-
B cell lymphoma (Hodgkin or non-Hodgkin)
- Hodgkin lymphoma- Reed-Sternberg cells that look like “owl eyes”
- A type of non-Hodgkin lymphoma- Burkitt’s lymphoma (B cell lymphoma of the jaw and face, endemic in children in malarial regions in Africa)
- Nasopharyngeal carcinoma, associated with Asian populations.
-
B cell lymphoma (Hodgkin or non-Hodgkin)
- Oral hairy leukoplakia: non-cancerous lesion in the mouth (associated with HIV patients).
Diagnosis:
- Paul-Bunnell test: antibodies can agglutinate the sheep red blood cells (hemagglutination by antibodies produced against EBV).
- Monospot test for rapid diagnosis (an improvement of the Paul Bunnell test), it is also called heterophile antibody test.
- Recent EBV infection is indicated by the finding of any of the following:
- IgM antibodies to the viral capsid antigen (VCA)
- Presence of VCA and absence of EBNA (EB nuclear antigen) antibody
- Rising EBNA titer
- Finding VCA and EBNA antibodies in the serum indicates that the person has had a past infection.
Treatment:
No effective vaccine or treatment. The best means of preventing infectious mononucleosis is to be exposed to the virus early in life- more benign in children.
If mistakenly given amoxicillin or ampicillin, the patient can develop maculopapular rash.
Pox virus (types)
- Small pox (variola):
- Inhalation and replication in the upper respiratory tract → dissemination by lymphatics (macrophages) → internal and dermal tissues were inoculated after second viremia → hemorrhage of small vessels of dermis, leading to rash and pox.
- Vaccinia virus (cow pox):
- Used for small pox vaccine → scratching live virus into the patient’s skin → sometimes encephalitis, progressive infection (vaccinia necrosum).
- Molluscum contagiosum:
- Benign, epidermal tumor (wart-like), acquired by direct contact → most common on the trunk, genitalia.
Treatment: liquid nitrogen or iodine.
Adenovirus
Double stranded DNA naked virus with icosahedral symmetry.
Transmission and infection:
- The virus is spreading by aerosol, close contact, or fecal-orally. It infects mucoepithelial cells in the respiratory tract, GI tract and conjunctiva or cornea causing cell damage.
- The virus persists in lymphoid tissue (tonsils, adenoids) and the virions are stable in response to drying, detergents, GI tract secretions.
Diseases:
- The most common cause of infection in the adenoids and tonsils.
- Follicular conjunctivitis: the mucosa becomes pebbled, inflamed (source: swimming pools)
- Epidemic keratoconjunctivitis: Occupational diseases for industrial workers, risk factors are irritation of the eye by foreign body and dust.
- Pharyngo-conjunctival fever: in young children with mild influenza-like symptoms- nasal congestion, cough, fever, chills, myalgia, headache.
- Acute respiratory tract disease: syndrome of fever, cough, pharyngitis, pneumonia- in military recruits.
- Other respiratory tract diseases: laryngitis, croup, bronchiolitis, pertussis-like illness in children.
- Gastroenteritis and diarrhea: in infants, 15% of the cases in hospitalized patients.
- Systemic infections in immunocompromised patients: encephalitis, pericarditis, pneumonia, hepatitis (exogenous or endogenous infection).
- Hemorrhagic cystitis (rare)
Diagnosis:
Cultivation in epithelial cells, HeLa cells; ELISA, PCR; CF, HAI
Treatment:
There is no known treatment, live oral vaccine in military recruits but not in civilian populations.
Non-obligatory vaccines
- Varicella zoster vaccine (live attenuated)
- HPV: Guardasil (inactivated recombinant vaccine)
- Adenovirus (live attenuated vaccine)
Obligatory vaccine
Hepatitis B vaccine
Causative agent of ‘gloves and socks syndrome’
Parvovirus B19 may cause a papular-purpuric “gloves-and-socks” syndrome (PPGSS), which manifests as an erythematous exanthem of the hands and feet with a distinct margin at the wrist and ankle joints.
Classification of diseases caused by virus:
- Acute infection (e.g. common cold)
- Acute infection + rare late complication (e.g. Measles, SSPE)
- Latent infection (e.g. VZV)
- Chronic infection (e.g. HBV)
- Chronic infection + late disease (e.g. HTLV-1 leukemia, HIV)
- Slow infection (e.g. prion: Creuzfeldt-Jakob, FFI)
