Viruses

VIRUSES:

• Obligate intracellular parasites
• Multiply in living hosts
• Infect all major groups (plants, animals, funi, bacteria)
• Metabolicallyinactive outside host cell - depend on host for replication
• Most viruses are host specific whilst some have broader range. Host range include:
  • Correct attachment - viral proteins need to bind to recepter on cell surface.
  • After virus enters, need right cellular machinery for viral replication. 
  • If replication can occur, decide if infectious viruses are able to get out of cell and spread infection. 
• Viruses are not made up of cells, so cannot replicate independently; grow, develop or generate metabolic energy.
• Have a remarkable ability to adapt over time - mutating glycoproteins in capsids/envelopes to get entry into host cells.
• Scientists talk about the number of infectious particles rather than the number of living particles. 

• Unique and simple molecules lacking cell structures and metabolic machinery.
• Diverse in appearance and size.
• Composed of 1 or more of either DNA or RNA, enclosed by a capsid (protective protein coat)
• Nucleocapsid = nucleic acid genome + capsid
• Genetic material = single or double stranded DNA/RNA (Linear or circular)
• Capsids - self-assembling proteins - icosahedral, helical or complex.
  • Helical - hollow protein cylinders - capsid proteins arranged in rod-like spiral around genome.
  • Icosahedral (polyhedral) - 20 triangular faces + 12 vertices - capsid proteins arranged in triangular units.
  • Complex - neither pureply icosahedral nor helical.
• Some contain additional membranous envelope outside capsid.
  • Consist of complex: carbs, lipids, proteins. 
  • Aquired from host cell - budding through host cell membrane. 

Continued... 

5 basic structural forms of viruses in nature...

• Naked icosahedral - poliovirus, hepatitis A.
• Naked helical (no human viruses) - tobacco mosaic.
• Enveloped icosahedral - herpes, yellow fever.
• Enveloped helical - rabies, flu, mumps, measles.
• 

Classification = Nature of Genome + Physical Structure

Nucleic acid

• RNA or DNA
• Single or double stranded
• Non-segmented or segmented
• Linear or circular
• If genome is single-stranded RNA, can function as mRNA?
• If genome is diploid (like retrovirsuses)

Virion structure:

• Symmetry (icosahedral, helical, complex)
• Enveloped or not enveloped
• Number of capsomers

- Secondary characteristice include replication stratedgy. Some single group viruses have a subgroup that may have a fundamentally different replication strategy. 

• Many viruses encode a few structural proteins - those that make up virion (mature virus particle) & maybe an enzyme that participates in replication of viral genome. 
• Other viruses can encode many more proteins - most participate in some way in replication but don't end up in mature virion.
• Can be cultured in lab by inoculating living host cells/cell lines.
• Virus concentration is determined from virion counts or number of infectious units.
• Can exist in 2 phases - extracellular and intracellular.
  • Extracellular - few enzymes - cannot replicate.
  • Intracellular - viral nucleic acids replicate and induce host metabolism to synthesise virion components. (Host biosynthetic machinery is hijacked to replicate virus particles)

General Sequence of virus replication process:

• 1) Infection of host through attachment, entry and uncoating.
• 2) Transcription of viral genes.
• 3) Replication of new nucleic acid.
• 4) Translation via protein synthesis.
• 5) Assembly of new virus
• 6) Release of mature virus. 

BACTERIOPHAGES [Bact - rod; phag - eat]

• A virus that infects bacteria - eg: E.Coli
• 2 types of life cycles - Lytic and Lysogenic.
  • Lytic - viral replication followed by hot cell lysis to release virus particles.
  • Lysogenic - viral genetic material incorporated into host genome and viral replication occurs later.
• Bacteriophage Lambda isable to carry out either lifecycle.
• 

Lytic Cycle (Virulent phages)

5 stages for bacteriophage lytic cycle...

1) Attachment - portions of capside combine with bacterial cell wall receptors (Lock & key manner)

2) Penetration - viral enzyme digests part of cell wall -  viral DNA injected into bacterial cell.

3) Biosynthesis - biosynthetic apparatus of host taken over - used for protein production of viral DNA and coat.

4) Maturation - DNA assembles and capsid protein occurs, producing 700 phage particles.

5) Release - Lysozyme (encoded for by viral gene) produced and disrupts bacterial cell wall - releases phage particles & causing host cell death. 

- During assembly - error: fragments of host DNA packaged in heads of viral particles. Bacterial genes may then be transferred by bacteriophage. This mechanism = generalised transduction. 

Lysogenic Cycle (Temperate phages)

• Infected bacterium doesn't start producing new virus particles immediately.
• Phage is latent - ie: not actively replicating - called a prophage
• After attachment and penetration - viral DNA integrated into host bacterial DNA.
• Prophage replicated within host DNA - all lysogenic cells (bacterial daughters) carry copy of viral DNA.
• Environmental factors - like UV radiation - may induce prophages to exit from host genome and induce a lytic cycle - thus producing new virus particles.

- During this exit, an error may occur: inclusion of 1 or more host cell genes viral genome. Genes replicated with viral DNA and packed into new virus coats - may be carried to new host cell and nextcycle of infection. This process is called = specialised transduction.  

- During lysogenic lifecyle - virus genes expressed as if host genes. In some cases, expression may alter host cell in novel ways. Eg: Phage conversion (bacteriophage introduces toxin, altering bacterial genome and expressed together with bacterial genes)

HIV - Human Immunodeficiency Virus

• HIV retrovirus [retro-backward, viro-poison]
• Complex retrovirus with genome of 2 identical positive, single stranded RNA molecules.
• AIDS (Acquired Immuno Deficiency Syndrome) - associated with HIV infection.

How infection occurs:

• Infects white blood cells - in human immune system -  which have CD4+ receptors on their host cell membranes (T-helper cells).
• HIV binds to CD4+ cell's co-receptors CCR5 or CXCR4- allowing virus entry into cell's cytoplasm - can replicate here.
• HIV uses various viral enzymes - transcriptase, protease, integrase - to incorporate itself into host's genome.
• Reverse transcriptase converts single stranded RNA genome to HIV double stranded copy DNA (cDna) - then integrated into host genome becoming a provirous - through action of viral integrase.
• Normal cellular DNA transcription happens - HIV derived mRNA also produced from HIV DNA in human DNA strand.
• Transcription of vDNA = new virus production - ie: biosynthesis, maturation, release.

• DNA never leaves host DNA in contrast to prophage. 
• Release also does not involve destruction of host cell - occurs through budding where part of host cell carried away by virus. 
• Aftter, HIV can infect more human CD4+ cells
• High decrease in CD4+ cells = loss of cell mediated immunity - causing body to succumb to opportunistic infections
• Reverse transcriptase is error-prone - incorporates 1 mutation per cDNA copy made. 
• High mutation rate + deteriorating immune system = immune system collapse ie: AIDS
• AIDS = collective name for several diseases resulting from a defective immune system.
• 10-15 years without treatment following infection.

EMERGING VIRUSES - Result of mutations - spreading from previously isolated community or changing hosts. eg: SARS (Severe Acute Respiratory Syndrome), Ebola, Zika, Flu variants.

GIANT VIRUSES - 'Mimivirus' - Pandora viruses = genomes large and contain mostly unrecognizable genes.