Chapter 25: Viruses

25-1 Viral Structure

25-2 Viral Replication

25-3 Viruses and Human Disease

I. Definition of a Virus (~ SMALLEST infectious particle, 20-250 nm)• NON-living particle w/a nucleic acid (DNA or RNA) and a protein coat.

25-1 Viral Structure

(1) Virology (~ Bacteriology)

• Study of viral structure and behavior, HOW disease occurs and WHY?

Critical Thinking(1) Based on your understanding of virus replication, how might virologists or microbiologists cultivate or artificially reproduce viruses in the laboratory?

II. Advent of Virology (what IS a virus?)• Wendell Stanley (1935) crystallized the TOBACCO MOSAIC VIRUS—suggested viruses were NOT made of CELLS.

II. Characteristics of Virology• Viruses are NOT accepted as being “organisms.” (e.g., “strains”)

(A) Viral Structure• 2 features—a nucleic acid AND a protein coat.

(1) Capsid (i.e., the protein coat)• Protein coat PROTECTING the nucleic acid.

(2) Envelope (STOLEN from HOST cell membrane)

• Lipid membrane surrounding capsid ALLOWS virus to infect host cells. • ENVELOPED viruses include flu, chickenpox, herpes simplex, and HIV.

(3) HIV (a.k.a. Human T-Lymphotropic Virus III or HTLV-III)• An enveloped RETROVIRUS (RNA) that INVADES human T-4 lymphocytes.

(4) Glycoproteins (sugar-protein viral SPIKES that act like “keys”)• Projections of ENVELOPE used to ATTACH and ENTER a host cell.

(B) Viral Shape (i.e., Capsid shape)• Determined by viral genes (2 common shapes exist).

(1) Icosahedron (e.g., Herpes, Chicken Pox, and Polio)• Viral capsid shaped with 20 triangular faces.

(2) Helical (e.g., Rabies, Measles, and Tobacco Mosaic Virus) • Viral capsid shaped like a coiled-spring.

IV. Grouping Viruses (shape and structure)• Grouped by ENVELOPE and TYPE of nucleic acid (DNA or RNA).

(A) Virus Types• DNA/RNA viruses differ in HOW they exploit the host cell’s machinery.

NOTE:

Upon INVADING the host cell, DNA viruses can EITHER…

(1) Directly produce RNA that makes more viral proteins, OR

(2) JOIN host cell’s DNA to direct the making of new viruses.

On the other side, RNA viruses…

(1) Release viral RNA into the host cells cytoplasm, thereby hijacking the host cell’s ribosomes to produce new viral

proteins.

(1) Retrovirus (e.g., HIV)• A class of RNA virus USING an enzyme called “reverse transcriptase.”

(2) Reverse Transcriptase (reverses the normal process of transcription)• Uses RNA to make DNA is integrated into the HOST CELL genome. NOTE: The DNA then makes an RNA transcript of itself, translating this RNA into proteins that are used to assemble NEW VIRUSES.

(B) Viroids and Prions (NO capsid NOR envelope)• SIMPLER than viruses, ~ smallest observed PARTICLES to replicate and cause DISEASE.

(1) Viroid (observed with infected CROP plants)• Short strand of RNA responsible for disrupting plant cell metabolism.

(2) Prions (LARGE cell surface mammalian proteins, ~ 250 AA)• Abnormal proteins CLUMP together inside a cell, BLOCKING cellular traffic leads to CELL DEATH.

NOTE: Scrapie (in sheep), Bovine spongioform encephalopathy (BSE or mad cow disease), is a fatal brain disease of cattle; in humans, known as Creutzfeld-Jakob disease (CJD).

I. Obligate Intracellular Parasites• Viruses replicate ONLY by invading a HOST cell and EXPLOITING organelles to produce MORE viruses.

25-2 Viral Replication

II. The Bacteriophage (a virus AGAINST bacteria cells)• Injects foreign DNA into bacteria WHICH gets integrated INTO host genome (e.g., T phages, infect Escherichia coli with USEFUL human genes)

III. The Lytic Cycle (FIVE stages)

• Virus INVADES host cell, MAKES new viruses, DESTROYS host cell, RELEASES new viruses.

(1) ATTACHMENT of virus to a SPECIFIC host cell

(2) ENTRY of viral DNA into host cell

(3) REPLICATION of viral DNA

(4) ASSEMBLY of NEW viruses

(5) RELEASE of NEW viruses from a lysed host cell

(1) Virulent (deadly, potent)• Virus that undergoes LYTIC cycle and causes DISEASE (i.e., cell death)

(2) Receptor Sites (Docking Sites)• Specific to HOST cell’s SURFACE viruses RECOGNIZE and ENTER.

(3) Lysis (during the RELEASE stage of the LYTIC cycle)• An ENZYME made by VIRAL genome causes HOST cell membrane to DISINTEGRATE, releasing new viruses.

(2) Shingles is a disease caused by the same herpes virus that causes chicken pox. How do you account for the fact that shingles often appears years later after the initial chickenpox attack?

Critical Thinking

IV. The Lysogenic Cycle• Viruses REMAIN inside HOST cell for an EXTENDED period of time, (sometimes YEARS), before triggering LYSIS.

(1) Temperate Virus (NOT virulent)• Undergoes LYSOGENIC cycle, and does NOT kill HOST cell immediately.

(A) Lysogeny in Bacteriophages• INSTEAD of immediately creating new RNA and viral proteins (Lytic Cycle), viral DNA integrates itself INTO host cell’s DNA.

(3) Lamda is a bacteriophage that attacks E. coli and may enter a lysogenic cycle. Once it enters the lysogenic cycle, the phage inhibits the entry of more phages. What do you suppose could be an evolutionary advantage to the phage of “immunizing” its host against further lambda infections.

Critical Thinking

(1) Prophage (can become VIRULENT through radiation and chemicals) • Bacteriophage DNA THAT integrated INTO host cell’s genome; (e.g., the prophage replicates WHENEVER host bacterium reproduces)NOTE: During LYSOGENIC cycle, prophage does NOT harm host cell; However, IF a prophage becomes VIRULENT, it will enter the LYTIC cycle, and eventually KILL the host cell.

(B) Lysogeny in HIV

• HIV replication in the T4 lymphocyte can be summarized as follows:(1) HIV attaches to the CD-4 receptor site and gains access inside cell.(2) Viral RNA is released from the HIV capsid into the cytoplasm.

(3) Reverse transcription makes a copy of HIV viral DNA (a PROVIRUS).(4*) Viral DNA is integrated in the host white blood cell’s genome.

(5) Viral RNA and proteins are produced for HIV assembly.

(6) New HIV viruses are assembled in the cytoplasm.

(7) Newly assembled viruses leave the cell through lysis or budding.

(1) Provirus• Viral DNA inserted into HOST nucleus for an EXTENDED period of time. NOTE: The lysogenic cycle ENDS when the PROVIRUS is TRANSCRIBED into RNA and TRANSLATED into viral proteins.

V. Evolution of the Virus• Possibly from DNA fragments of EARLY cells? (These DNA fragments may have entered host cells through a damaged cell membrane). NOTE: Viruses (having a genome), ARE able to MUTATE QUICKLY, and alter their IDENTITY which helps to EVADE immuno-recognition.

I. Infectious Diseases (viruses are SPECIFIC to cell types)

• Effects range from FEVER, to CANCER, to FATAL diseases.

NOTE: Transmission of viral infections is SIMILAR to bacterial infections and depends on ENVIRONMENT.

25-3 Viruses and Human Disease

• Examples include the common cold, chickenpox, MMR, polio, rabies, and hepatitis.

(4) People who have had a hepatitis B viral infection have a greater chance of developing liver cancer later in life, especially if they are exposed to aflatoxin. Aflatoxin is a mold toxin found in some foods, such as contaminated peanuts. What does this relationships suggest to you about the role of the hepatitis virus in causing cancer?

Critical Thinking

II. Prevention and Treatment• CONTROL of viral diseases is accomplished in TWO ways:

1. VACCINATION and 2. ANTIVIRAL drugs.

(1) Antiviral Drugs (SMALLER supply than ANTIBIOTICS)• Designed to interfere with viral nucleic acid synthesis. (either DNA or RNA)

(A) Types of Virus Vaccines • Introduction of pathogens (or parts) to STIMULATE immune system to provide IMMUNO-MEMORY.

(1) Inactivated Virus (used to make vaccines, works MOST of time)• Injected virus does NOT replicate in the host’s system.

(2) Attenuated Virus (MOST successful—better LONG-term immunity)• Genetically altered virus that CANNOT cause disease.

(B) Smallpox Eradication Program (~WHO in 1967)• Strict quarantines AND vaccination; ended in 1980 with no apparent cases of virus. (LAST smallpox case occurred in Somalia in 1977).

(C) Other Antiviral Approaches (recent research)• Controlling ANIMAL VECTORS that SPREAD viral diseases.

(i.e., mosquitoes in West Nile Virus, and spreading MEAT with an oral RABIES vaccine for wild wolves and coyotes in the Western U.S).

(1) Acyclovir (interferes with viral REPLICATION)• Antiviral drug with success against HERPES and CHICKENPOX.

(5) Some people suggest that the drug AZT can help patients infected with HIV. Knowing that this drug blocks the enzyme reverse transcriptase, suggest a reason why AZT might help HIV infected patients.

Critical Thinking

(2) Azidothymidine (AZT, successful against retroviruses)

• Inhibits REVERSE TRANSCRIPTASE of retroviruses, including HIV. (AZT interferes with the synthesis of viral DNA and RNA)

(3) Protease Inhibitors (used with AZT to slow HIV to AIDS)

• Interfere with the synthesis of viral CAPSIDS during replication.

NOTE: Antibiotics are SPECIFIC to bacterial machinery and are NOT effective in the treatment of viral diseases.

(6) Based on your understanding of HIV structure and replication, suggest one way to interrupt the replication of HIV.

Critical Thinking

III. Emerging Viruses (an ecological perspective)

• Viruses OFTEN exist in ISOLATED habitats, BUT spread when these habitats are DEVELOPED by HUMAN ACTIVITY.

(e.g., Ebola virus emergence in the tropical forests of the Congo; Hantavirus in southwestern U.S.; Machupo virus in South America, Lassa fever virus in Western Africa, and HIV in South Africa).

IV. Viruses and Cancer (virology MEETS oncology)• Research CANCER genes can be TURNED-ON by LYSGOGENIC viruses. (e.g., HPV Cervical Cancer AND Hepatitis-B Liver Cancer )

Revisiting Cell Structure and Function

• Viruses depend on cells to replicate and that this viral dependence on cells affects cell structure and function.

Assessing Prior Knowledge

• Describe the accepted criteria to be classified as a living thing.

• Summarize the major steps involved in protein synthesis, noting the locations of each process.