Viruses in animal cells show a variety of infection patterns:
Lytic infection:destroys host cells.
Persistent infection: host cell continues to shed virus over a long time. Cell gradually becomes recognizably poorer (recognized as a cytopathic effect, or CPE), eventually “crumps out”.
Transformation: infection by certain viruses causes cells to change, become cancerous. Responsible genes are called oncogenes (tumor-producing genes). Viral oncogenes have also been found in uninfected cells. These are genes involved in regulation of cell cycle; when defective, normal regulatory control is lost and cell can become cancerous.
Latent infection: virus genes may not be expressed for long time (ex. many Herpes infections). Not the same as lysogeny –genes are not integrated into host chromosome.
Human Immunodefiency Virus (HIV) and AIDS
AIDS first recognized in 1981. Over 300,000 cases reported in U.S., over 8 million in Africa, over 12 million infected world-wide.
View AIDS in perspective: a PBS website with current data on the AIDS epidemic.
Transmission: sexual activity, especially with multiple sex partners. Also contaminated blood, needles, hospitals. Not just a disease of homosexuals! In Africa (most # cases) about equal of male and female victims.
AIDS lowers immune system’s ability to respond to other infections, allows opportunistic pathogens to invade body. Most common infection is pneumonia (lung infection) caused by Pneumocystis (2/3 of all AIDS patients get this at some point).
Host cell for the virus is CD4 (T-helper) cell, needed to activate antibody production. In normal human, CD4 cells account for 70% of total T cells –in AIDS, number decreases, may reach 0% of T cell pool.
Progress of HIV infection only recently understood. Formerly thought that virus became latent. Now discover that virus is anything but latent: during infected period (which can last 10 years), body is destroying ~ billion virions/day, and virus is killing about 100 million CD4 T cells a day. HIV virus continues replicating, and body rapidly replenishes lost T cells. Only when lymph nodes wear out does virus gain the upper hand. See handout in class titled “Huge HIV turnover helps explain drug resistance, pathogenicity”.
Prognosis: with carefully selected treatments, better than before. Virtually every infected person dies sooner of later, usually within 10 years of infection. No cure known, no vaccine yet available. Virus mutates rapidly, many strain variations. Vaccines being tried, results mixed but preliminary.
Drugs: some types of drugs offer limited success.
AZT (azidothymidine) is analog of thymidine, but is blocked at 3′- position, so no further chain growth possible. These target viral reverse transcriptase enzyme. Should reduce DNA synthesis in treated cells. But eventually, viral mutants resistant to drug arise. Also, long term use of drug can cause toxic side effects.
protease inhibitors. Like many viruses, HIV needs to cleave large protein product into smaller products, using viral protease protein. By inhibiting this enzyme, should block necessary stage in viral replication cycle. Still under development, but resistant viral mutants to these types of drugs have already been found. Still, drug offers promise. See handout article for more details. Safe sex! Caution with sharps. Extra caution in clinical settings.
HIV Life Cycle (budding through plasma membrane)
Viroid and Prions
Viroids very small ssRNA genomes (~300 nucleotides). No coat, and RNA does not encode protein. Known viroids cause diseases in plants because host cells replicate the RNA.
Prions (protein infectious agent) do not have a nucleic acid genome. Prion diseases are often called spongiform encephalopathies because of the post mortem appearance of the brain with large vacuoles in the cortex and cerebellum.
Prion diseases in humans are probably primarily a genetic neurotoxic disorder. Transmission of the disease to humans via infectious prions is likely to be rare.
The prion is a modified form of a normal cellular protein known as PrPc (for cellular), found predominantly on the surface of neurons and thought to be involved in synaptic function.
The modified form of PrPc (= prion) is known as PrPsc (for scrapie) which is relatively resistant to proteases and accumulates in cytoplasmic vesicles of diseased individuals. Prion protein may cause normal protein to fold abnormally.