Microbiology lecture note terminology

Oncogenic viruses

Transformed cell

Integration of DNA into the host cell. Permissive cell produces virus, non-permissive cells get transformed in DNA viri. RNA viruses can transform permissive cells.

RNA oncogenic virus

Retroviridae. Can transform permissive cells. May not transform permissive cells. Retroviruses carry transduced cellular oncogenes. These oncogenes have NO role in viral replication.

DNA oncogenic virus

Papova, adeno, herpes, hepadna, poxviridae can cause transformation. Can replicate in certain cells of the natural host w/o producing a tumor. Simian virus-40 can live in monkey kidneys w/o any problems, but cause tumors in hamster neonates.

Cell growth patterns

High cell density. Increased rate of growth. Decreased requirement for serum growth factors. Enhanced ability to grow in semisolid medium. Anchorage independent *. Loss of contact inhibition

Cell surface alteration

Some viral proteins will be moved to cell membrane. Surface antigen

Tumorigenicity

Production of tumor when transformed cells are injected into animals. A transformed cell is not necessarily oncogenic. NO in vitro growth characteristic can succedssfully predict tumorigenicity

Highly oncogenic

Carry cellular oncogenes

Weakly oncogenic

Do not carry oncogenes, but modify cell to become oncogenic

Cellular transformation

Introducing new transforming genes into the cell. Induction or alteration of gene expression from a pre-existing cellular gene

Transduction by a retrovirus

Recombination between cellular protooncogene w/ viral genome. Captured cell gene gets mutated and transcribed under strong viral signals

Insertional mutagenesis

Retroviral promoter inserted before a cellular proto-oncogene. Results in enhanced expression of the cellular proto-oncogene. Under influence of viral enhancer sequence

Proto-oncogene

Genes that can become oncogenic under the influence of the proper signals.

Oncogene activation by translocation

Chromosomal translocation of a proto-oncogene from its normal location to near a strong promotor which activates a proto-oncogene

Cis activation

Activation gene is next to gene that is activated. Viral gene is next to oncogene

Trans activation

The activator is not near the gene that is activated

Gene amplification

An increase in number of copies of a certain gene will result in increassed amount of gene product

Ocnogne activation by Mutations

Alteration in proto-oncogene due to mutations or deletions will alter the product

HTLV-1

RNA tumor virus. Human T-cell lymphotropic virus causes cutaneous T-cell leukemia. Expresses large quantities of IL-2 membrane receptors. Is expressed at very low levels. Detected by presence of viral DNA and proteins in malignant cells. Transmission unknown

Tax genes

Carried by transregulating retrovirus. Neceassary for viral replication and may be oncogenic. Proviral sequences found in the DNA of the T-cell and not in the normal cells. In endemic areas (S. Japan, Caribbean and SE USA), upto 10% of the people carry antibodies to HTLV-1 v. 1% in the rest of the world.

Rb and P53

Can form complexes w/ viral gene products that cause transformation. Except for parvoviridae, all DNA containing viruses can cause transformation

Polyomaviruses

Along w/ SV40, the best characterized DNA containing tumor virus. Code for large T, middle T and small t antigens. Large T complexes w/ P53 and Rb genes. Middle t antigen is membrane bound and complexes w/ c-src protein and activates tyrosine kinase

SV40

Codes for Large “T” and small “t” antigens. T-Ag is found tightly complexed w/ cellular tumor suppressor gene product P53 and Rb. Small portion of t-antigen is bound to the cell membrane

BK virus

Not known to cause human disease

JC virus

Virus is regularly isolated from PML patients. Not associated w/ human disease. Found in tumors

PML

Progrssive multifocal luco

Papillomavirus

Majority of vulvar, carvical, and penile cancers. Carry HPV-DNA (HPV-16 and HPV-18) and some other cases exhibit DNA from HPV-11, 31, 33 and 35. tobacco smoke and coinfection w/ herpesvirus have been involved in the progression of HPV lesions to carcinomas

Adenovirus

Rodent cells and induce specific early antigenic proteins localized in the nucleus and the cytoplasm of the transformed cells

E1A

Early protein complexes iw/ the Rb protein

E1B

Protein binds to the cellular protein P53

HHV-1,2 and 5

Can transform hamster cells w/ low frequency.

HHV 2

Associated w/ carcinoma of cervix. No herpesvirus-induced transforming genes has yet been found

???HHV-4

Infects B-lymphocytes and in immuno-deficient individuals, the infection may progress to B-cell lymphomas. Linked to Burkitt's lymphoma.

Poxviruses

Molluscum contagiosum virus produces small benign growth in humans. Very little is known about the proliferative disease. A poxvirus-coded growth factor that is related to epidermal growth factor and to transforming growth factor may be involved.




Viral Respiratory infections

Nasal terbinate

Foster removal of large particles

Nose-alveoli temperature dif

4 degrees centigrade. Most viruses stay in the upper cooler area

Ciliated epithelia

Clear material upwards out of respiratory tract

Goblet cells

Secretes mucins. IgA will also be secreted

Clara cells

Secrete a protease which activate the viral fusion factor required for entry of some virus particles

Macrophages

Found in alveoli. Clear alveoli of debris because they do not have mucous or ciliated cells. Also found through the rest of the respiratory system

Granular cells

Produce surfactants

Nasal response to virus

Epithelium becomes swollen and edematous producing congestion and fluid accumulation.

Gingival, buccal cavity and nasopharynx

Sights of viral localization

IgG and IgA

Predominant antibodies in the lower and upper RT. IgA dominates upper tract. IgG dominates lower tract. Both found everywhere.

IL-6

Reverts IgA producing plasma cells to B-cells. Produced in response to influenze

Receptor sites

Ubiquitous throughout the host

Budding

Apical or basal budding decides the course for the spread of the virus through the body. Restricted to surface or spread through the body.

Environmental factors

Temperature, humidity, crowding and size of infecting dose

RSV

Respiratory synctial virus. Infection of young people. Enveloped virus (less stable than naked virus). MOST COMMON LRT in pediatrics. 3 antigenic types. Usually acquired from adults w/ subclinical URT infection w/ RST. Main protection from IgA in upper respiratory tract. In infants under 6 months, the virus rapidly moves to LRT producing profuse inflammation, monocyte infiltration, and interstitial pneumonia w/ syncitium formation. Diagnosis by IF (immunoflourescence) or ELISA. Reinfection occurs and immunity increases. Occurs largely in winter. Ribavirin, given in aerosol in severe cases. Vaccine in development

Direct contact

Method of RSV spread.

Aerosol

Measles virus. Sneezing and coughing

Sneeze

100 to 2000um particles at 100 ft/sec to 2-5ft

Cough

850 ft/sec

Normal flora

Micro-organisms living in the upper RT w/o disease production. Herpes virus

Professional invaders

Those that will attack healthy tissue. Influenzae and rahbda virus??. Adhere to normal mucosa. Interfere with ciliary action. Resist destruction by macrophages. Damage mucosal and submucosal tissue

Secondary invaders

Attack hosts that have impaired defenses. Staph aureus and strep pneumoneiae. Damaged respiratory cells, local impairment of defenses due to chronic respiratory illness, chronic irritants (bronchitis, foreign bodies, tumors), reduced resistance resulting from old age, alcoholism, renal impairment, and reduce immune response

Acute

Replication only in respiratory mucosa (influenza, corona-, rhino, parainfluenza viruses

Persistent

Spread to lymphoid tissue and tonsils (adenovirus)

Systemic

RT infection spreads to other organs (mumps, measles, herpersvirus)

CPE??


Common cold

Rhinoviruses and coronoviruses are the cause of more than 50% of the cases. Coxsakie A-, echo-, adeno-, influenza, parainfluenze respiratory syncycia. Diagnosed by clinical picture. Identification of causative agent for epidemiology is by ELISA.

Picronaviridae

Class IVa. Binds to ICAM-1 and is endocytosed. One particle can establish infection. Upper RT infection. Human to human transmission. Incumbation 2-3 days. Symptoms last 3-7 days. Asymptomatic carriers. No known reservoirs

Corona virus

25-30nm. Upper RT. Class IVb. Enveloped virus w/ helical nucleocapsid. Envelope is made of ER and golgi. Secreted by cellular secretory mechanism and by cell destruction. Isolated to humans, no cross infections w/ animals. Patchy destruction of ciliated epithelium. Restricted to URT. Incubation is longer than rhinovirus. Low-grade fever, rhinorrhea, cough, sneezing and runny eyes. World wide infection of all ages. 87-100% of healthy individuals have antibodies to the identified serotypes. Reinfection of the same serotype possible because neutralizing antibodies are short lived. Peak incidence in winter and spring.

Pharyngitis/Tonsilitis

Usually caused by either damage to the respiratory mucosa or by inflammatory response in the lymphoid tissue.

Adenoviruses

Class I, w/ penton fibers. Icosahedral, naked virus w/ fibres attached to each penton. Immediate early proteins push cell to S phase. More than 100 serotypes. Neutralizing antibodies against the fibres. Causes broad range of disease.

Endemic adenovirus

Transimission by respiratory and feco-oral route. Symptoms include fever, pharygitis, tonsilitis and cough. Zoryza, vomiting, diarrhea, meningeal signs and pulmonary infiltrate in 50% of patients. Pediatric respiratory infection 2-7% by age 2 and 50-70% have neutralizeing antibodies against serotypes 1 and 2.

Sporadic adenovirus infection

Pharyngo-conjunctival fever (PCF). In swimming pools w/o adequate chlorination. Swimming pool only leads to conjunctivitis w/o pharyngitis. Caused by serotypes 3, 7. fever lasts for 3 to 4 days after 5 to 7 days incubation. Headache, fever (103 degrees), malaise, anorexia, sore throat.

Epidemic adenovirus infection

Serotypes 8 and 19. ocular morbidity, chronic w/ permanent visual impairment. Incubation 3 to 21 days, lasts for ~2 weeks. Unilateral or bilateral conjunctival infections.

ARD

Adenovirus. Upto 80% of military recruits. Civilians have limited occurance. Transmitted by respiratory droplets. Fever, malaise, nasal congestion, sore throat, hoarseness, headache and cough

Adenovirus in immunocompromised

Mostly in lungs but can spread anywhere.

CF most useful

4 fold rise in antibody titer. Isolation of wirus from throat of feces.

Adenovirus vaccines

**Serotypes 3, 4, 7 and 21. oral live attenuated virus. Spread to close contracts is not significant

Adenovirus epidemiology

World wide, temperate zones, unclean environments (feco-oral transmission).



Parainfluenza virus

4 types of antigens. Cross react and elicit heterotypic antibodies. Type 1 and 2 in late summer and fall. Type 3 throughout the year. IgA is short lived. No real treatment or vaccines.

Otitis media

Infection of middle ear, the sinuses and the epiglotis occur by direct extension of infectious agents from the nasopharynx. Mostly caused by a variety of viruses. Can cause dissyness

Laryngitis

Viral infections are the main source. Parainfluenza and RSV

Traneitis

Viral infections are the main source. Parainfluenza and RSV

Acute bronchitis and bronchiolitis

Both bacteria and viruses cause the condition. Damage cilia caused by viruses in the URT allow bacteria to establish. Loss of cellular integrity may allow extension of infection into bronchioles and alveolar spaces

Chronic bronchitis

Caused by a combination of normal flora (secondary invaders) and irritants such as ciggarette smoke and air pollution

Bronchiolitis

Largely in children. Occlusion of narrow bronchioles. 2/3 or more of the cases are due to RSV. Emerging milder disease – metapneumovirus

Paramyxovirus of turkeys

A pneumovirus. Causes bronchiolitis in infants upto 2 years of age. Inflammation of bronchioles but milder disease than RSV. Complications due to CF and chronic lung disease. 38 cases w/ 3 deaths in Brisbane. Baby does not want to eat. IF or RT-PCR

Influenza virus

2 different peplomers w/ different activities. Binds to sialic acid containing glycoproteins. Transcriptional complex is transported to the cell nucleus. Viral polymerase cleaves 10-13 nucleotides from the newly synthesized host mRNA from the 5' end and uses this capped RNA as a primer for the synthesis of viral mRNA (cap stealing). Another mRNA is synthesized that serves as a template for the negative strand RNA.

Influenza internal antigens

Nucleoproteins can be used to classify into groups A, B, and C

Influenza external antigens

Inlfluenza A can be divided into subgroups based off of surface antigens. Hemagglutinin and Neuraminidase

Hemagglutinating antigen

15 different antigenic types have been identified in birds and animals for influenza A. In contrast, influenza B is found only in humans. HAs are responsible for attachment of viirons to cell. Fusion activity, and stimulation of neutralizing antibodies.

Neuraminidase

Enzymatic activity that allows for virus to burst out easier. 9 antigenically distinct surface glycoproteins have been identified for influenza A. All influenza B have cross reaqcting NA

Antigenic drift

Only in influenza A. STILL CROSS REACT

Antigenic shift

Influenza A. mutations or gene reassortment. Animal reservoirs can be a reservoir for new pandemics

Influenza pathogenesis

NO production is inhibited --> No clearance of bacteria. NA destroys mucus allowing HA mediated endocytosis. Kill mucus cells and causes them to desquamate

Influenza manifestations


Influenza complications

Primary viral pneumonia, secondary bacteria infections, Reye syndrome, Guillain-Barr syndrome

Reye's syndrome

??. Caues brains to swell. Aspirin can trigger syndrome in kids w/ influenza virus or chicken pox.

Guillain-Barre syndrome

Can occur from the vaccine for influenza virus as well as from the virus itself.

Influenza diagnosis

IF, ELISA, and HAI (four fold rise in the antibody titer)

Epidemic threshold

Concept provided a method of estimating the number of influenza virus infections in the community without virus isolation and laboratory identification

Vaccination for influenza virus

Not very effective. Strain specific. May not correctly predict the strain that will emerge. Types of vaccines: inactivates whole virus, split virus, attenuated virus. Loss of concentration, insomnia, nervousness, anxiety, confusion, drowsiness.

Amantidine

Block the ion channels formed by influenza A. does not work against influenza B. Resistant mutants arise frequently.

Rimantidine

Block the ion channels formed by influenza A. does not work against influenza B. Resistant mutants arise frequently.

SARS

Severe acute respiratory syndrome. Cause unknown.

Avian influenza

22 cases in humans. 75 out of 1100 had eye problems due to avian influenza virus.