Mod. 18 Viruses, Viral, Treatment, Prions

Obligate Intracellular Parasites

Only replicate host cell

Few or no enzymes of own for metabolism - mainly use host

Host Range

Viruses infect every Known organism

Most can only infect specific cells of one host species

• Viruses that infect bacteria are called a bacteriophage or phage

• Determined by receptor specificity

Phage therapy

Phage therapy

Use phage to treat bacterial infections

Problem: cells are different + immune system kills phage

Structure

Nucleic Acid

Protein capsid - protein coat that surrounds the nucleic acid

May contain an envelope around capsid - made up of lipids, proteins, carbohydrates

Old system of taxonomy

Based on symptoms (human) or similar morphologies

May cause more than one disease state

Look the same but dramatically different in actions

New system of taxonomy

Nucleic acid

Strategy of replication

Morphology

Classification is “new” and changing

Viral species

Same genetic information

Same host range

No specific epitet - use common name

Lytic or T-even

Attachment - phage attaches to host cell wall

Penetration - penetrates cell via phage lysozyme and injects DNA

Biosynthesis - phage DNA directs synthesis of viral components by host cell - eclipse period

Maturation - components assembled into virions

Release - cell lyses (phage lysozyme) and virions released

Lysogeny

Attachment (cell wall) and penetration (inject)

Can then continue with lytic cycle OR

DNA sometimes integrates with bacterial DNA - this is called a prophage

• Bacteria can reproduce normally (divide) - prophage genes repressed

• Phage conversions can happen

• Occasionally, viral DNA exercises from bacterial DNA and then continues with lytic cycle

Life cycles

Lytic

Persistent infections - not completely cleared

• Latent

• Chronic

Latent infections

Virus remains in host for long periods w/o producing disease (repressed state)

Chronic

Small amounts of virus always found - slow producing virus factory

HIV

Attachment

Use a receptor on plasma membrane of host cell

No tails - attachment sites over whole surface of virus

Penetration

Endocytosis

Fusion

Endocytosis

Plasma membrane folds inward to form vesicle which virus is in - loses envelope

Fusion

Envelope fuses with plasma membrane and releases capsid

Uncoating

Enzymatic removal of capsid proteins

Biosynthesis/assembly

Animal viruses do not always express genes using the normal flow of genetic information (DNA to RNA to protein)

Assembly varies from happening in the nucleus to happening in the cytoplasm

Retrovirus - RNA turned into DNA that integrates and follows Dogma

• Reverse Transcriptase

What would a dsDNA virus do?

Genetic Pathway (Replication, Transcription, Translation)

What would a ssDNA virus first do?

Make ssDNA and turn it into dsDNA

What would a +ssRNA virus do?

Make proteins and more RNA

acts like mRNA

What would a -ssRNA virus first do?

Package enzyme to make +ssRNA in order to make -ssRNA and proteins

Lysis

Nonenveloped

Budding

Enveloped

Hard to diagnose, why?

Most do not cause cancer

Cancer may not develop immediately

Cancers are not contagious

Oncogenes in animal cells

Any gene that causes the cell to grow/divide again and when mutated causes cancer

Causes for activation

• Mutagenic chemicals

• UV light

• Oncogenic viruses

  • 10% of all cancers

  • Activated by virus integration into DNA

  • Transformation of the cells - tumors

Characteristics of Tumors

Uncontrolled growth

No contact inhibition

Decreased cell adhesion

Viral diseases

60% of infectious diseases world-wide are caused by viruses and only 15% is bacterial

90% US population suffers from viral disease/year

Very few antiviral therapies

Nucleoside analogs

Nucleotide make-up without the phosphate

Interfere w/ DNA and RNA synthesis

Examples

• Ribavirin

  • Hepatitis C and respiratory syncytial virus

  • Includes high mutation rate of RNA virus

• Zidovudine

  • HIV treatment

  • Competitive analog blocks synthesis by reverse transcriptase

  • Fairly toxic

• Acyclovir

  • Herpesvirus - shingles treatment

  • Activity - Virus infected cells use drug in place of normal nucleotides which leads to DNA synthesis issues

  • Administered orally, topically, or injected

Enzyme inhibitors

Nevirapine

• HIV treatment

• Inactivates reverse transcriptase

Indinavir and saquinavir

• HIV treatment

• Protease inhibitors

Raltegravir and elvitegravir

• Integrase inhibitors

Fusion or exit inhibitors

Enfuviritide - Stops HIV fusion (to Cell)

Olsetamivir (Tamiflu), zanamivir (Relenza), peramivir (Rapivab)

• Prevent influenza virus release

Interferon

Natural product of the immune system which stimulates cells to produce antiviral proteins

Alpha - interferon

Hepatitis C treatment

Prions structure

Proteinaceous infections particle

Cause rare neurodegenerative disorders

• Diseases with long incubation periods

• Always fatal (progressive)

Prion Diseases

Scrapie—sheep

Mad cow disease

Kuru—humans

Creutzfeldt-Jakob disease (CJD)—humans

Gertstmann-Straussler-Scheinker syndrome—humans

Fatal Familial Insomnia—humans

Chronic Wasting Disease—deer

Transmission of Prions

Eating CNS tissues from an infected animal

Transplanting nerve tissue

Contaminated surgical instruments - hard to degrade via enzyme of heating

Mode of action for Prions

Can induce abnormal folding of normal cellular prion protein in the brain

Causes large vacuoles in the brain —spongiform encephalopathy

Viroids structure

Short pieces of naked circular RNA

• 300-400 nucleotides long, no protein coat

Causes plant diseases