Immunology and Virology - prima parte

CLASSES OF TUMOR VIRUSES

Both viruses are able to integrate their genomes within cellular chromosomes. Such integration is not, however, a pre-requisite for tumor formation.

DNA tumor viruses

DNA tumor viruses have a DNA genome that is transcribed into RNA which is translated into protein. They have two life-styles:

• In permissive cells, all parts of the viral genome are expressed; this leads to viral replication, cell lysis, and cell death.
• In non-permissive cells, viral DNA is usually, but not always, integrated into the cell chromosomes at random sites; only part of the viral genome is expressed. This is the early control functions of the virus: viral structural proteins are not made and no progeny virus is released.

Examples:

• Papilloma Virus: the important genes in the transformation are E6 and E7 (Early genes). It's integrated only part of the virus.
• Adenovirus: highly oncogenic virus; The Early genes involved are E1A region and E1B region.

systems that intensify the mutations collection. →- Human immunodeficiency virus -1 and 2 (HIIV-1 and HIV-2) gene tat trans-activatorSarkoma’s sarcoma, lymphomas→- Hepatitis C virus (HCV) Hepatocellular carcinomaExamination Questions- Viral genetics- Effects of viral infection on host cells: lytic infection- Effects of viral infection on host cells: persistent, latent infections- Effects of viral infection on host cells: transforming infection (oncogenic viruses: mechanisms ofaction)EPIDEMIOLOGY: TRANSIMISSION, GEOGRAPHICAL AND SEASONAL FACTORSOutbreaks, epidemics and pandemics mean different things.Viral pathogenesis is due to 2 different factors:- The invasive ability of the virus (the virulence of the virus itself)- The host’s immune response (if we are in presence of immunocompromised host, the viralpathogenesis is very strong)If we consider a disease due to a virus, we have to consider those 2 factors, which leads to:• The break of the natural

protective barrier (immune system)

Ex. Coronavirus enters via airborne and it starts its colonization in the nose-pharyngeal epithelium (in which we have mucosa). It's able to fight against this innate immune system, reaching the cells, starting from enter in the blood and be transferred in every target organ of the organism, the brain, in which it's able to kill (the main one the neural cells).

• The kill of the cells of an important organ (the brain is the main one!)
• The trigger of a destructive immune response: sometimes our immune system answers in a strong way (immune pathogenesis due to the immune system)

The virus can survive in different environments for different periods of times (can influence the transmission), but the only environmental factor in an invasive ability can be the temperature (viruses don't survive in cold environments). The viral pathogenesis due to the structure of the virus, which change with the environment.

BASIC

STEPS IN THE VIRAL DISEASE:

1. Acquisition: the virus enters into the body throughout the mucosa (pharyngeal, nasal, intestine, etc.) "primary vaginal epithelium in which is usually observes the first replication of the body, called site". In this step we can observe the activation of innate response: when we have a good one, we usually are asymptomatic (with no symptoms) or pauci-symptomatic (with small symptoms) and sometimes, many infections are stopped at this step. "secondary
2. Incubation period: the virus may spread to a site". Sometimes the patient can be asymptomatic or can produce non-specific symptoms (Prodromic period). Usually, from the primary site, the virus can pass into the blood: throughout viremia (means that we have the virus in the blood) the blood brings the virus to the target organs (secondary organs).
3. Replication in the target tissue: here we can get a very host strong response by the immune system (immunopathogenesis). Many viruses are

produced (contagium): in this moment we have the very disease of the infection, which usually produces serious damages against the virus. People in this step are usually more contagious than in other steps!

4. Resolution of infection (finished) or a persistent/chronic infection: our immune system is not (HIV, Hepatitis B/C, Herpes Virus, ...) able to fight the virus, to eliminate it completely

ROUTES OF TRANSMISSION

The virus can be transmitted throughout:

• Direct transmission: due to a personal contact between an infected person and a healthy one (sexual transmission), or personal-animal contact (zoonosis: infectious agents pass from animal to humans, with a direct contact), usually throughout droplets (small drops emitted when we speak, talk, sneeze, cough, ...)
• Indirect transmission: due to indirect contact (fomites), such as all the contaminated droplets...), (surfaces, objects, or other kinds of vehicles like food and water (gastrointestinal tract), insect bites

It is necessary the presence of the sensitive cells (susceptible cells to the virus, that express the VAP on the membrane) and permissive cells in the primary site.

Entry sites can be:

• Mucosa (epithelial cells): our mucosa is covered by mucous layer, very important for the protection against the virus infection, as the virus must penetrate it to reach the cells; is one of the parts of the immune system.
• Skin (ex. Papilloma Virus, provoke the warts)
• Infected syringes, ...
• Parenterally (bite of insects/mammals, ex. Rabies Virus, Togavirus, Bunyavirus, ...)

When the virus reaches the primary site, it starts the local replication, which can be stopped/slowed by the immune system; the cells produce Type I interferons (called "cytokine"), that induce antiviral state in not yet infected cells.

In the cytoplasm we have specific receptors that can feel the abnormal presence of those interferons; in this way, a signal enters the nucleus and the cells start to produce Type I