1. Viral Pathogenesis

2. Viruses by definition can replicate only inside living cells.
The first manifestations of viral infections are seen at the cellular level.
Following initial exposure to some viruses may include rapid onset of observable symptoms, which is referred to as an acute infection.
Alternatively , the initial infection by other viruses may be mild or asymptomatic.
The initial infection by certain viruses is followed by one of two alternative outcomes of medical significance :
1-establishment of persistent infection.
2-establishment of a latent infection.

3. Viral pathogenesis at the cellular level
Cells show variety of different responses to viral infection depending on the cell type and the virus.
Many viral infections cause no apparent morphologic or functional changes in the cell
When changes do occur , several responses can be recognized :
1-Cell death:
A cell can be directly killed by the virus. in most cases this is due to the inhibition of synthesis of
cellular DNA , RNA and protein. Example of viruses that kill their host cell are adenovirus and poliovirus.

4. -Transformation2
Some viruses can transform normal cells into malignant cells. Transformation is an irreversible genetic process caused by the integration of viral DNA into the host’s DNA. 3-Cell fusion : infection of cells with certain viruses causes the cells to fuse producing giant multinucleate cells. Example herpesviruses and paramyxoviruses 4-Cytopathic effect ( CPE) : CPE is a catch-all term that refers to any visible changes in appearance of an infected cell .

5. Initial infection
Following initial multiplication at the primary site of entry , the viral infection may remain localized , or may become disseminated.
The infection may be asymptomatic(unapparent)
Alternatively , typical symptoms of disease may occur , often in two temporally distinct forms :
1-early symptoms at the primary site of infection.
2-delayed symptoms due to dissemination from the primary site causing infection of secondary sites.

6. The severity of the disease is not an absolute characteristic of particular virus species . Instead it is influenced primarily by the effectiveness and type of host defense mechanisms , and the virulence of the infecting virus

7. Routes of Entry and Dissemination to Secondary sites
Common routes by which viruses enter the body are essentially the same as for bacterial infections through:
Skin, the respiratory tract , the gastrointestinal tract , or the urogenital tract

8. Some viruses remain localized and cause disease at the primary site of infection
Viruses can disseminated through out the body ,and infect cells at secondary sites characteristic for each specific virus type , thus causing the disease typically associated with that species .
the presence of virus in the blood is termed viremia

9. 1-skin
Introduction through the skin usually a break in the surface of the skin from an abrasion or cut , or by inoculation of the agent by an insect , animal bite , or needle
2-Respiratory tract: those viruses that enter the body via the respiratory tract and remain localized produce symptoms that primarily in the respiratory passages
(Rhinoviruses) ( causing common cold
other inhaled viruses spread systemically after the primary infection , and produce a characteristic disease due to the infection of cells at secondary sites for example measles and chicken pox.

10. 3-Gastrointestinal tract
Viruses infecting via the GI tract follow characteristic “fecal-oral” transmission pattern ,those viruses that remain localized in the cells of the GI tract may cause symptoms such as diarrheal disease, for example ,enteric adenoviruses or rotaviruses , However many viral infections that remain localized in the GI tract are aysmptomatic
Some viruses that infect via the GI tract enter the lymphatic system and the blood, then can cause symptomatic disease unrelated to the GI for example ,in the liver(hepatitis A) or the CNS (poliovirus)

11. 4-Genital tract
Viruses infecting by this route are transmitted primarily during sexual contact .
spread of the virus can affect nongenital tissues, such as CNS ,where herpes virus may cause meningitis or encephalitis
Typical secondary sites of localization
A-skin: Viremia can result in a rash due to infection of cells in the epithelium .This type of rash contains infectious virus.
B-Central Nervous system
The most common route by which viruses infect the CNS is one whereby virus-carried by the blood-infects endothelial cells of the cerebral vessels , and ultimately is released into the brain itself.

12. Alternatively ,virus can be released from endothelial cells into the cerebrospinal fluid at the choroid plexus .A less common ,but important route of viral spread is the axonal migration of virus from peripheral nerve endings directly into the CNS (Rabies virus)

13. 5- fetus -The fetus represents a special ,but very important ,site for secondary localization of virus infections. -virus from the maternal circulation infects cells of the placenta ,thereby gaining access to the fetal circulation and to all of the tissues of the developing fetus - Neonatal infection can also occur during birth when the fetus comes in contact with infected genital secretions of the mother.

14. Virus Shedding and Mode of Transmission
The mode of transmission of a viral disease is largely determined by the tissues that produced progeny virus ,and /or the fluids into which they are released
A-Skin
In only a few instances are skin lesions the major source of transmissible virus , warts (papilloma viruses) being the prime example
A number of diseases are characteristized by virus –containing skin lesions ,but are transmitted by virus shed from another site for example chicken pox ,transmitted mainly by the respiratory route.
B-Respiratory tract
The respiratory route is the obvious mode of transmission of viruses causing respiratory disease . shedding of virus from the respiratory tract that provides virus both for viremic spread to other organs and for transmission to other host.

15. C-Gastrointestinal tract
All those viruses whose portal of entry and primary site of replication are via the GI tract are shed from the infected host in the feces.
d- body fluids
Some viruses are shed from the host in one or more body fluids ,for example urine , semen, milk and blood

16. Factors Involved in Termination of The Acute Infection
In a typical uncomplicated ,acute infection ,virus is totally eliminated from the host in two to three weeks .This outcome is primarily a function of the host’s immune system , with involvement of both cell-mediated and humoral responses .
The relative importance of these two responses depends upon the virus and the nature of the disease

17. A- cell mediated responses the earliest immune system responses to virus infection are a generalized inflammatory response ,accompanied by nonspecific killing of infected cells by natural killer cells . This latter activity is enhanced by interferon and other cytokines and begins well before the virus –specific immune response. Later, cytolysis by virus specific cytotoxic T lymphocytes that recognize virus peptides displayed on the cell surface ,also eliminates infected cells
These cellular responses are especially significant in that they help to limit the spread of the infection by killing infected cells before they have released progeny virus

18. B-Humoral response
Circulating antibodies may be directed against any of the virus protein
Humoral antibodies also take part in killing infected cells by two mechanism
1-antibody –dependent , cell –mediated cytotoxicity
2-complement –mediated lysis

19. Persistent infections:
A persistent (chronic)infection is one in which virus present continuously –usually at a low level –over an extended period of time after the acute infection and disease have ended .
Latent infections :
A latent infection is usually distinguished from a persistent infection by the fact that virus is not demonstrable continuously ,but instead episodes of active virus replication and cell killing alternate with periods when no infectious virus or evidence of virus replication is present.