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Flashcards in Midterm IV (Leiel) COPY Deck (26):
1

Classification of viruses by morphology

  1. Helical shape: helical array of capsid proteins (capsomeres) around a helical filament of nucleic acid (DNA or RNA).
  2. 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.
  3. Prolate shape: elongated icosahedron (e.g.: head of bacteriophages), cylinder shaped with cap at either end.
  4. 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).
  5. Complex: capsid is neither purely helical nor icosahedral.  

2

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.

3

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 invasionretrograde axonal flow to dorsal root ganglialatency (non-replicating state)

It remains latent in the trigeminal ganglia, and with a proper provocative stimulireactivation.

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).

4

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).

5

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.

6

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).

7

Classification of viruses by nucleic acids

Classification according to the Baltimore Classification of viruses:

  1. dsDNA (e.g. Herpes simplex virus)
  2. ssDNA (parvovirus)
  3. dsRNA (e.g. reovirus)
  4. +ssRNA (e.g. Enterovirus)
  5. –ssRNA (e.g. Influenza A virus)
  6. ssRNA (Retrovirus)
  7. Nicked dsDNA (e.g. Hepatitis B virus)

8

Cultivation of viruses in the lab

Cultivation is in embryonated egg, or monolayer cell tissue.

Culture media:

  1. Liquid or semi liquid
  2. Components: serum, nutrients (amino acids and carbohydrates), vitamins, growth factors, antibiotics and an indicator.
  3. Sterilization by filtering to avoid contamination (which can be by mycoplasma or other bacteria, fungi or endogenous viral infections).

9

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.
  • 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.

10

Pox virus (types)

  1. 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.
  2. Vaccinia virus (cow pox):
    • Used for small pox vaccine → scratching live virus into the patient's skin → sometimes encephalitis, progressive infection (vaccinia necrosum).
  3. Molluscum contagiosum:
    • Benign, epidermal tumor (wart-like), acquired by direct contact → most common on the trunk, genitalia.

Treatment: liquid nitrogen or iodine.

11

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:

  1. The most common cause of infection in the adenoids and tonsils.
  2. Follicular conjunctivitis: the mucosa becomes pebbled, inflamed (source: swimming pools)
  3. Epidemic keratoconjunctivitis: Occupational diseases for industrial workers, risk factors are irritation of the eye by foreign body and dust.
  4. Pharyngo-conjunctival fever: in young children with mild influenza-like symptoms- nasal congestion, cough, fever, chills, myalgia, headache.
  5. Acute respiratory tract disease: syndrome of fever, cough, pharyngitis, pneumonia- in military recruits.
  6. Other respiratory tract diseases: laryngitis, croup, bronchiolitis, pertussis-like illness in children.
  7. Gastroenteritis and diarrhea: in infants, 15% of the cases in hospitalized patients.
  8. Systemic infections in immunocompromised patients: encephalitis, pericarditis, pneumonia, hepatitis (exogenous or endogenous infection).
  9. 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.

12

Non-obligatory vaccines

  • Varicella zoster vaccine (live attenuated)
  • HPV: Guardasil (inactivated recombinant vaccine)
  • Adenovirus (live attenuated vaccine)

13

Obligatory vaccine

Hepatitis B vaccine

14

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.

15

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)

16

Cytopathogenic effects caused by viruses

Caused especially by naked viruses

  • Cell lyses
  • Forming body inclusions (Herpes, Rabies)
  • Forming syncytium
  • Vacuolization
  • Apoptosis
  • Haemadsorption: the infected cells adsorb red blood cells
  • Transformation (tumor)

17

Varicella Zoster virus

A virus from the Herpes virus family, enveloped.

Primary infection in the mucosa of the respiratory tract (respiratory droplet transmission) → blood stream and lymphatic system → spreading viruses to the skin → dermal vesiculopustular rash → chicken pox → latent form in sensory ganglia (dorsal root ganglia) → reactivation (immunocompromised, stress) → virus migrates along neural pathways to the skin → herpes zoster (shingles)

Chicken pox is characterized by fever, headache, and vesicular rash.

In chicken pox- vesicles are in different stages (in small pox- vesicles are in the same stage).

Shingles (caused by reactivated virus) is characterized by rash with dermatomal distribution, postherpetic neuralgia, vision loss (herpes zoster ophthalmicus).

Congenital varicella syndrome: limb hypoplasia, cutaneous dermatomal scarring, blindness.   

*chicken-pox in adults - pneumonia, encephalitis (especially in immunocompromised.

Diagnosis:

Organ biopsy, scrapings, fluorescent antibody methods

Treatment, prevention, control:

As in HSV, varicella-zoster immunoglobulins, live attenuated vaccine, acyclovir / femcyclovir / Valacyclovir for treatment.

18

Papilloma virus

Naked, double stranded DNA virus with icosahedral symmetry.

Can spread by sexual contact, and fomites.

HPV 1,4:

Verruca vulgaris (cutaneous common wart) - physical contact

HPV 6,11:

Laryngeal papillomatosis (recurrent respiratory papillomatosis)

Condyloma accuminatum (anogenital warts)

HPV 16,18:

Anogenital cancers (also HPV 31,33)

Vaccine- Guardasil (inactivated recombinant vaccine), for HPV 6, 11, 16, 18

Virulence factors:

  • E6 protein- associated with proteolysis of p53 (cell cycle checkpoint regulator, stops transition from G1 to S phase).
  • E7 protein- Rb (retinoblastoma protein, tumor suppressor) is targeted by E7.

HPV breaks down P53 and Rb so infected cells lose the checkpoint that prevents them from moving from G1 to S phase, resulting in uninhibited cell growth and neoplasia.

Screening for cervical cancer is done by Pap smear, where koilocytes can be identified.

19

Parvovirus

Parvovirus B19 is the only Parvovirus that can cause human disease; it is a naked virus, single-stranded DNA virus (unlike all other DNA viruses which are double-stranded).

Parvovirus is the smallest DNA virus, and has icosahedral shape.

It targets immature cells in the erythroid lineage, transmitted by respiratory droplets.

There are 2 types of parvovirus:

  1. Autonomous parvovirus: do not require helper viruses, can replicate by themselves
  2. Adeno-associated virus: require helper viruses to replicate

Disease:

Erythema infectiosum (Fifth disease/"Slapped cheek" disease): initial febrile stage and second symptomatic stage → "slapped cheek", the rash starts on the face and moves downward.

In adults the disease manifests as joint pain, arthritis and edema. Aplastic anemia can appear in sickle cell patients (caused by depletion of the bone marrow).

In utero: hydrops fetalis (vertical transmission from mother to fetus).

Diagnosis:

PCR, IgM detection, ELISA.

Treatment:

No treatment, no vaccine.

20

List enveloped viruses

Herpes viruses, Pox virus, Hepatitis B virus

21

Molluscum contagiosum- causative agent, treatment

Caused by a member of small pox virus family

Benign, epidermal tumor (wart-like), acquired by direct contact → most common on the trunk, genitalia.

Treatment: liquid nitrogen or iodine.

22

B19: the disease

The disease caused by parvovirus B19 is erythema infectiosum (Fifth disease/"Slapped cheek" disease): initial febrile stage and second symptomatic stage → "slapped cheek", the rash starts on the face and moves downward.

23

Experimental animals: advantage and disadvantage

Advantages:

Provides the environment in which viruses usually grow; all the necessary nutrient, growth factors, etc. are present.

Disadvantages:

Can be contaminated by other causative agents (e.g. bacteria, fungi, other viruses, etc.); killing of animals.

24

HHV-6

HHV-6 is a DNA virus from the Herpes virus family.

It infects CD4+ cells, causing immunosuppression; the disease is named roseola (or exanthema subitem) and is characterized by fever that lasts usually for 4 days.

Children with roseola can develop febrile seizures.

After the fever, a diffuse lacy body rash occurs, that spares the face.

The virus affects children at ages 6 months to 2 years, and is usually self-limiting.

Treatment:

  • There is no approved medicine so the treatment is supportive.
  • Supportive: cooling + fluids

25

Virus causing diarrhea

Adenovirus

26

HHV-8

HHV-8 is a part of the Herpes virus family, double-stranded DNA virus that causes Kaposi sarcoma.

Kaposi sarcoma is associated with AIDS patients and immunosuppressed patients. It causes lesions on the nose, extremities, and mucous membranes due to proliferation of vasculature (caused by dysregulation of VEGF). Kaposi sarcoma might be confused with basillary angiomatosis caused by Bartonella hensleae.

Lesions can be found within the GI tract, most commonly occurs on the hard palate.

Infection of B cells can cause primary effusion lymphoma (B cell lymphoma).

Transmission: sexual contact.

Treatment:

  • antiretroviral therapy if the patient is HIV positive and hasn't started it yet