Metabolically inert, genetic particle. Needs to infect a host cell in order to reproduce.

(see pictures on pg. 3.4: fig. 3.6, 3.7, 3.8)

They are classified according to whether they are RNA or DNA viruses.

They are also classified according to whether they are naked or enveloped viruses.

LIFE CYCLE OF VIRUSES

1.) Attachment and Penetration

Specific Attachment.: A receptor on the virus (either a peplomer or capsomer) interacts and binds to a receptor on the surface of the host cell. (See pg. 3.6 fig 3.11 for a list of host cell surface receptors). Viruses are very specific about their host cells this specificity is determined by these attachment receptors.

Entry.: Viruses must now get their genetic information into the cell. They can either (1) punch a hole into the cell (2) fuse their envelope with the cell's membrane or (3) become phagocytosed by the cell. (See pg. 3.6, fig. 3.12 for cartoons on how viruses get into cells.)

2.) Viral Genome Expression and Replication

In DNA viruses, mRNA is made off of viral DNA by host cell RNA polymerase. In RNA viruses, a viral RNA polymerase (which comes in with the nucleocapsid) can make mRNA from the genome. Retroviruses are special case because these viruses carry reverse transcriptase. Reverse transcriptase makes DNA off of an RNA template. These viruses can thus make a DNA copy of their RNA genome and this DNA can become integrated into the host's genome (see below).

The viral mRNA is used to make viral proteins like viral enzymes, capsomeres and peplomeres. These accumulate inside the cell. The viral genome is also replicated many times.

3.) Assembly and Release of New Virus Particles

This is autocatalytic. The genomes associate with capsomeres to form nucleocapsids. Enveloped virus nucleocapsids then bud out of the cell membrane, thus acquiring an envelope. (Peplomere proteins become inserted into the membrane before budding.) (See pg. 3.9, fig. 3.16 for a diagram of how influenza virus buds through the host cell membrane.)

THE OUTCOME OF VIRAL INFECTION

(1) The cell may lyse or be destroyed. This is usually called a lytic infection and this type of infection is seen with influenza and polio. (2) Alternatively, the virus may reproduce at a slow rate and be shed by the cell for a very long time. These virus infections are called persistent and this can be typical of hepatitis B infections. (3) Other viruses may enter a dormant state and not replicate until some trigger causes them to activate and become either persistent or lytic. These virus infections are called latent, and this is typical of HIV and herpes virus infections.

Persistent and latent infections may occur if the viral genome becomes integrated into the host cell genome. (Very similar to the example we saw with the F plasmid in the Hfr E. coli cells). When a virus does this it is called lysogeny and such viruses are called lysogenic viruses. The integrated viral genome is called a provirus (or a prophage if it is a bacterial virus).

The phenotype of bacteria can be changed or transformed by such lysogenic viruses and some of these cases are important medically. Corynebacterium diptheriae only produces diptheria toxin if is infected with a phage carrying the toxin gene. A similar situation exists with Clostridium botulinum and botulism toxin and Streptococcus pyogenes and erythrogenic toxin - the toxin which provokes scarlet fever.

Viruses and Cancer

Lysogenic viruses may also infect human and other animal cells. Some of these viruses are now known to be able to provoke the development of cancer.

Cancer cells have two major characteristics which make them different from the other cells around them: (1) they have uncontrolled growth and (2) they appear immature or dedifferentiated.

In normal cells, growth regulation and differentiation processes are controlled by oncogenes (or c-oncogenes), and if an oncogene becomes mutated, cancer may result.

Several lysogenic viruses have been shown to carry oncogenes (v-oncogenes). The v-oncogenes are often mutated forms of their c-oncogene counterparts. Viruses are believed to have captured the oncogenes from cells and the oncogenes presumably give the virus some reproductive advantage.

If such a virus infects a cell and then integrates itself into the cell's genome, the v-oncogene may lead to the transformation (transformation = cancer phenotype) of the cell.

One way that cells protect themselves from the effects of mutated c-oncogenes or imported v-oncogenes is thru the action of tumor suppressor genes. Although several tumor suppressor genes have been reported, the best known is a gene called p53.

The gene product of p53 looks for mutations on the cell's DNA and if it finds one it (1) starts a set of reactions which stops DNA replication or (2) starts a set of reactions which lead to apoptosis (programmed cell death) if the DNA damage cannot be reapaired.

Human Lytic Viruses:

Smallpox (Variola) - Repiratory and then systemic. (Last known "natural" case in Somalia 1977. There was a laboratory acquired case later).

Respiratory Syncytial Virus (RSV) - Severe lung infections in infants. Infects respiratory tract but spread by contact. Handwashing is important.

Adenovirus - Mild to severe infections of the respiratory tract, Eye infections and gastrointestinal infections.

Rhinovirus - "Common cold virus" infects the upper respiratory tract.

Norwalk Virus - Gastroenteritis in older children and adults. Fecal-oral transmission.

Rotavirus - Gastroenteritis in infants and young children. Fecal-oral transmission.

Measles (rubeola) - Repiratory infection first and then systemic

Rubella (german measles) - Respiratory first and then systemic. Congenital infections are a serious concern.

Influenza Virus - Severe respiratory infections. Three serotypes: A, B and C. Serotype A also infects birds and other mammals where it trades genetic information with bird and mammal strains of influenza virus. Giving aspirin to children with influenza and chickenpox may lead to Reye's syndrome.

Polio Virus - Infects the GI tract first then through the blood to the central nervous system. Spread by oral-fecal route.

Rabies Virus - Spread by the saliva in the bite of an infected animal. Infects muscle cells at bite site then moves to the central nervous system and the salivary glands.

Hemorrhagic fevers- A number of viruses cause damage to the small blood vessels causing hemorrhage throughout the body: Ebola - spread by blood and body fluids, reservoir unknown;Lassa Fever - spread by rodent urine and feces and also by blood and body fluids of infected individuals; Dengue Fever (breakbone fever)- spread by mosquitoes that have bitten infected people; Yellow Fever - spread by mosquitoes that have bitten infected people or infected monkeys.

Hepatitis A and E - Transmitted through fecal-oral route. Infects the intestine and then through the blood to the liver.

Human Lysogenic Viruses

Herpes Viruses:

Herpes simplex - infects epithelium of mouth or genitals then travels up nerve axons to become latent in ganglia of the spinal column. Neonatal infections are very severe. Spread by secretions from active lesions.

Varicella-Zoster Virus - Causes both chickenpox and shingles (herpes zoster). Shingles is the manifestation of a latent infection. Spread by the respiratory route.

Epstein-Barr Virus (EB virus) - Causes mononucleosis which is spread by contact with infected saliva. Initially infects the oral or genital mucosa but then spreads to B-lymphocytes. This virus is associated with two malignancies: Burkitt's lymphoma and nasopharyngeal carcinoma.

Cytomegalovirus (CMV) - Infection from contact with infected saliva and other secretions. The virus infects mucous epithelium and white blood cells. Many children and adults harbor latent infections which are totally assymptomatic. Immunocompromised people may suffer devastating lung, central nervous system and other systemic infections.

Papilloma Virus - These viruses cause a variety of warts and they are spread by close contact. Three types (16, 18 and 31) have been associated with cervical and penile cancers.

Hepatitis B (HBV) - Spread through saliva and all other secretions and also vertically (from mother to child during birth or rarely in utero). Severe infection of the liver. Some people may develop chronic hepatitis and become life long carriers of the virus. This virus is strongly associated with liver cancer (hepatocellular carcinoma).

Retrovirus - Both Human Immunodeficiency Virus (HIV) and Human T-cell Lymphotropic Virus-1 (HTLV-1) belong to this group. These viruses infect T-cells and are spread by blood and body fluids. HTLV-1 is notable for two reasons: (1) it is transmitted to infants through mother's milk and (2) it causes adult onset T-cell leukemia.