The group of viruses that cause human disease are the animal viruses. Disease can be either: generalized or systemic, or organ/site specific (e.g. neural, respiratory, skin, eye, liver, salivary gland, gut, STD).

Animal viruses go through the following steps during an infection and replication.

early phase
1. Adsorption - here the virus binds to the host cell membrane either non-specifically or through certain receptors.
2. Penetration - membrane fusion or induced phagocytosis

eclipse phase
3. Replication - host metabolism is commandeered by viral enzymes; virus takes over DNA/RNA synthesis; viral nucleic acids and proteins are then produced.
4. Assembly - DNA/RNA condenses and is packaged in capsid. This process may take place in the cytoplasm or in the nucleus depending on the virus.

late phase
5. viral particles are released either by budding (where virus picks up host lipid membrane) or cell lysis.

Treatment for viral infections is difficult because the viruses uses host machinery. Antiviral drugs usually consist of DNA or RNA analogs so that viral polymerases incorporate these chemicals into viral nucleic acids, or, alternatively, they are compounds that preferentially inhibit viral enzyme activity.

Pathogenesis of Viral Diseases (Chapter 30)
There are over 300 known viral diseases of man.

a) many infections are subclinical
b) the same disease may be produced by a variety of viruses.
c) the same virus may produce a variety of disease
d) the disease may bear no relationship to viral mrophology
e) the outcome in most cases reflects the genetic makeup of the virus and the host.

Steps in pathogenesis (see Figure 24:1):

1) Entry and replication in host cells. Most viruses enter their hosts through the mucosa of the respiratory or gastrointestinal tracts (major exceptions are those viruses that enter directly through needle sticks the bloodstream e.g. hepatitis and HIV, or those that are introduced by insect vectors, e.g. arboviruses).
2) Viral spread and cell tropism. Many viruses produce diseases at distant sites to where they entered. Most viruses spread via the bloodstream or the lymphatic system. When the virus is in the bloodstream it is called viremia. The viremic phase is generally short. Some viruses spread via the nervous system; e.g. rabies virus (this is how rabies gets to the brain). Cell tropism generally reflects specific receptors on the cell that the virus binds to; e.g. CD4+ receptors on T cells are recognized by HIV.
3) cell injury and clinical illness. Destruction of virus-infected cells is partly responsible for the clinical illness. Clinical illness is a complex mix of factors though, many of which are unknown.
4) recovery from infection. The host either sucumbs or recovers. Recovery involves both humoral and cell mediated immunity, and the production of interferon and other lymphokines. Acute infections are generally associated with viral clearance, however, there are many times when the host becomes persistently infected.
5) virus shedding. This is the last stage in pathogenesis where the virions are shed into the environment. Some viral infections (e.g. rabies in humans) represent dead-end infections, and shedding does not occur.

Host Immune Response
Both the humoral and cell-mediated components of the immune response are involved in the control of viral infections. Viruses illicit tissue responses that are different from those of pathogenic bacteria. Whereas PMNs (i.e. granulocytes) represent the primary cellular response from acute inflammation caused by pyogenic bacteria, infiltration with mononuclear cells and lymphocytes (agranulocytes) characterize the inflammatory reaction to uncomplicated viral infections.

Virally-encoded proteins constitute targets for the immune response. Virally-infected cells can be lysed by cytotoxic T cells due to the recognition of viral antigens on the cell surface. Humoral immunity protects the host against reinfection by the same virus. Also, neutralizing antibody operates against viral infections probably at the stage of attachment or uncoating. Secretory Ab also protects mucosal sites.

Small Pox Virus
The pox viruses are the biggest viruses known. They are enveloped double stranded DNA viruses. Small pox is caused by the variola virus.

There are three types of small pox virus: major, intermediate, and minor.

Disease: The virus is spread by the respiratory route, where droplets containing the virus (that originate from pustules) are inhaled by the host. The virus then invades the epithelium and moves to the lymph nodes where it replicates. The virus then leaves the lymph nodes causing a primary viremia. From the blood the virus then infects the RES cells, where it again replicates. It enters the blood again, causing a secondary viremia. Now the first symptoms appear (fever, malaise) and the skin rash begins (red, raised lesions) at 9-12 days after the infection. The patient is now contagious. The rash progresses to papules (serum-filled blisters) to pustules which break and release virus in 4-6 days. In 2-4 weeks, the pustules crust over and heal (many secondary bacterial infections occur in these lesions). Scarring is due to damage to the dermal layer of the skin. Death (20-50% of the time) usually resulted from infections with variola major which was more virulent than variaola minor.

Europeans have premunition to the disease (i.e. a genetic ability to resist disease due to many generations of viral contact). Natives of North and South America do not have premunition, so the disease was much more severe in these populations.

Smallpox is the only infectious disease to be eradicated through the intervention of man. The last case of smallpox was in Africa in the 70Õs. The vaccine has not been used in over 20 years. The disease was eradicated because:

1) smallpox only occurs in man.
2) a safe and effective vaccine was developed.
3) there was no vector borne transmission.
4) symptoms precede contagion (allows infected people to be quarantined).
5) the virus was antigenically stable.

Herpes Viruses (see Figure 24:2) The herpes group are enveloped double strand DNA viruses. They tend to become latent, and often exist for a lifetime within the host with no apparent symptoms.

Chickenpox
Caused by Varicella-Zoster virus. Very similar to smallpox but clinically much less severe. It was once considered a benign childhood disease that infected every child. Adult infections are much more severe.

Transmitted by the respiratory route, the infection progresses to the lymph nodes and then enters the blood stream causing viremia. The virus eventually lodges in the epidermal layer of the skin and a mild rash occurs. Virions are shed from 1 to 3 days before the rash until the rash disappears. The virus then moves to the neural ganglia and becomes latent (see Figure 24:3). Reactivation, usually in an old adult, results in shingles with skin lesions very siilar to chicken pox but this time localised in areas innervated by the infected neural ganglion. This form of the disease is extremely painful and may take several months to clear up.

Herpes Simplex Types I and II
Both are enveloped viruses and are extremely common in the US. Up to 90% of adults have antibody titers to Type I and 30% of adults are infected with Type II. Generally, Type I is spread by the respiratory route, whereas Type II is spread sexually. Both viruses become latent, and survive in neural ganglia (see Figure 24:4). Both diseases recur periodically, and the reccurring lesions last up to a month.

Herpes Type I (respiratory)
Diseases caused:

1) cold sores (fever blisters, some chancre sores)
2) keratoconjunctivis - the leading cause of acquired blindness in the US.
3) encephalitis - rare, but fatal.

Herpes Type II (sexual)
Diseases caused:

1) genital lesions (approximately 3 x 10 7 victims in the US; > 10% of the pop).
2) infant herpes - infant becomes infected following birth through an infected birth canal. Often fatal.
3) cervical cancer - strong association with infection.
Why do they recur? DonÕt know but recurrence is associated with sunburn; steroid therapy; stress; trauma; other diseases; menstruation; magic.

Treatment is restricted to topical oinments containing drugs; e.g. acyclovir which is a nucleic acid analogue. Only provides symptomatic relief. No vaccine available.

Epstein-Barr virus
This is an enveloped double stranded virus that causes infectious mononucleosis. This is transmitted by direct contact and the respiratory route. Most common in young adults, and the severity of the disease is related to the general health of the patient.

Disease: the virus gains access through the oropharynx where it multiples in epithelial cells and the salivary glands. Then the virus infects B cells and causes polyclonal activation of the B cells. Long incubation period from 30 - 50 days. The virus can become latent and may cause "chronic fatigue syndrome" (Yuppies disease). College students are at high risk because they are stressed, over extended and have contact with lots of new people.

EBV causes BurkittÕs lymphoma (cancer of the jaw) in black populations and nasopharyngeal cancer in Chinese males. These groups have a genetic predisposition for these forms of cancer.

Bed rest is the best treatment. There is no vaccine.

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