Viruses, Viroids, and Prions

Viruses, Viroids, and Prions

Viruses

  • Viruses are obligate intracellular parasites.
  • They cannot live outside a cellular host.
  • Existing medical therapies cannot treat or cure viral infections.
  • Viruses can infect:
    • Plants (causing variegation)
    • Animals
    • Bacteria (bacteriophages)
  • Viruses typically infect only one specific cell type due to viral tropism and the necessity for specific receptors on the host cell.

Viroids

  • Viroids are the smallest known pathogens.
  • They consist of naked, circular, single-stranded RNA molecules.
  • Viroids do not encode proteins.
  • They replicate autonomously when introduced into host plants.

Viral Structure

  • A viral particle is called a virion.
  • A virion consists of:
    • A protein coat (capsid)
    • A nucleic acid core (DNA or RNA)
    • An envelope (occasionally)

Viral Replication

  • In a laboratory setting, viruses can be replicated through:
    • Cell culture
    • Fertilized eggs
    • Living animals

Capsid Structure

  • Each capsid is made of identical protein units called capsomeres.
  • The protein coat surrounding the nucleic acid core is termed the capsid.
  • Capsomeres bond together to give the capsid its symmetry.

Capsid Arrangements

  • Helical Symmetry:
    • Protein subunits and nucleic acid are arranged in a helix.
  • Icosahedral Symmetry:
    • Protein subunits assemble into a symmetric shell covering the nucleic acid core.

Nucleic Acid Core

  • Viruses are characterized by their nucleic acid core, which can be:
    • DNA: double-stranded (ds) or single-stranded (ss)
    • RNA: double-stranded (ds) or single-stranded (ss)

Genetic Information

  • Genetic information flow:
    • Replication: Genetic information transferred vertically to the next generation.
    • Transcription: DNA to RNA.
    • Translation: RNA to protein.
    • Recombination: Genetic information transferred horizontally between cells of the same generation.

Viral Classification

  • Classification criteria:
    • Type of nucleic acid (DNA or RNA)
    • Symmetry of capsid
    • Naked or enveloped
  • Examples of families include:
    • Reoviridae (dsRNA, naked, icosahedral)
    • Picornaviridae, Caliciviridae (ssRNA, naked, icosahedral)
    • Flaviviridae, Togaviridae, Coronaviridae (ssRNA, enveloped)
    • Retroviridae (ssRNA, enveloped, produce DNA)
    • Paramyxoviridae, Orthomyxoviridae, Bunyaviridae, Arenaviridae (ssRNA, enveloped, helical)
    • Parvoviridae (ssDNA, naked)
    • Papovaviridae, Adenoviridae (dsDNA, naked)
    • Hepadnaviridae, Herpesviridae, Poxviridae (dsDNA, enveloped)

Viral Families and Genera

  • Parvoviridae:
    • Single-stranded DNA, nonenveloped, 18-25 nm
    • Human parvovirus B19 causes fifth disease and anemia.
  • Adenoviridae:
    • Double-stranded DNA, nonenveloped, 70-90 nm
    • Mastadenovirus causes respiratory infections and tumors.
  • Papovaviridae:
    • Double-stranded DNA, nonenveloped, 40-57 nm
    • Papillomavirus causes warts and cervical cancer.
    • Polyomavirus
  • Poxviridae:
    • Double-stranded DNA, enveloped, 200-350 nm
    • Orthopoxvirus (vaccinia and smallpox viruses) causes smallpox.
    • Molluscipoxvirus causes molluscum contagiosum.
  • Herpesviridae:
    • Double-stranded DNA, enveloped, 150-200 nm
    • Simplexvirus (HHV-1 and -2) causes fever blisters.
    • Varicellovirus (HHV-3) causes chickenpox and shingles.
    • Lymphocryptovirus (HHV-4) causes infectious mononucleosis and Burkitt's lymphoma.
    • Cytomegalovirus (HHV-5)
    • Roseolovirus (HHV-6 and HHV-7)
    • Rhadinovirus (HHV-8)
  • Hepadnaviridae:
    • Double-stranded DNA, enveloped, 42 nm
    • Hepadnavirus (hepatitis B virus) causes hepatitis B and liver tumors; uses reverse transcriptase.
  • Picornaviridae:
    • Single-stranded RNA (+ strand), nonenveloped, 28-30 nm
    • Enterovirus includes polio-, coxsackie-, and echoviruses.
    • Rhinovirus (common cold virus) is the most common cause of colds.
    • Hepatitis A virus
  • Caliciviridae:
    • Single-stranded RNA (+ strand), nonenveloped, 35-40 nm
    • Hepatitis E virus, Norovirus cause gastroenteritis.
  • Togaviridae:
    • Single-stranded RNA (+ strand), enveloped, 60-70 nm
    • Alphavirus diseases include EEE, WEE, and chikungunya.
    • Rubivirus (rubella virus) is transmitted by the respiratory route.
  • Flaviviridae:
    • Single-stranded RNA (+ strand), enveloped, 40-50 nm
    • Flavivirus diseases include yellow fever, dengue, St. Louis, and West Nile encephalitis.
    • Pestivirus, Hepatitis C virus
  • Coronaviridae:
    • Single-stranded RNA (+ strand), enveloped, 80-160 nm
    • Coronavirus causes upper respiratory tract infections and the common cold; SARS virus, MERS-COV.
  • Rhabdoviridae:
    • Single-stranded RNA (- strand), enveloped, 70-180 nm
    • Vesiculovirus, Lyssavirus (rabies virus) are bullet-shaped viruses with a spiked envelope; cause rabies.
  • Filoviridae:
    • Single-stranded RNA (- strand), enveloped, 80-14,000 nm
    • Filovirus (Ebola and Marburg viruses) are enveloped, helical viruses.
  • Paramyxoviridae:
    • Single-stranded RNA (- strand), enveloped, 150-300 nm
    • Paramyxovirus, Morbillivirus (measles virus)
    • Paramyxoviruses cause parainfluenza, mumps, and Newcastle disease in chickens.
  • Deltaviridae:
    • Single-stranded RNA (- strand), enveloped, 32 nm
    • Hepatitis D depends on coinfection with hepadnavirus.
  • Orthomyxoviridae:
    • Multiple strands of RNA (- strand), enveloped, 80-200 nm
    • Influenza virus A, B, and C; envelope spikes agglutinate red blood cells.
  • Bunyaviridae:
    • Multiple strands of RNA (- strand), enveloped, 90-120 nm
    • Bunyavirus (California encephalitis virus), Hantavirus are associated with rodents.
  • Arenaviridae:
    • Multiple strands of RNA (- strand), enveloped, 110-130 nm
    • Arenavirus causes lymphocytic choriomeningitis, Venezuelan and Lassa fever.
  • Retroviridae:
    • Single-stranded RNA, produce DNA, enveloped, 100-120 nm
    • Oncoviruses cause leukemia and tumors; Lentivirus (HIV) causes AIDS.
  • Reoviridae:
    • Double-stranded RNA, nonenveloped, 60-80 nm
    • Reovirus, Rotavirus cause respiratory infections transmitted by arthropods; Colorado tick fever.

Viral Stability and Mutation

  • Most Stable Viral Form: viruses with dsDNA genome, example Herpesviridae. The process involves dsDNA to mRNA, then mRNA is translated into protein, combined with capsomeres to produce dsDNA.
  • Most Mutation Prone: viruses with +ssRNA genome, example Ebola virus. The process involves +RNA genome being converted to -RNA, then back to +RNA, then mRNA encodes the capsomere for protein production.

Viral Envelopes

  • Many viruses that infect mammals are enveloped.
  • All envelopes have a phospholipid bilayer.
  • Envelopes arise from the plasma membrane of the infected host cell.

Viral Replication Cycle

  • Attachment: Virion attaches to host cell.
  • Entry and Uncoating: Virion enters the cell, and its DNA is uncoated.
  • Biosynthesis: Viral DNA is replicated, and viral proteins are made.
  • Maturation: Virions mature.
  • Release: Virions are released.

Lytic Infections

  • The host cell fills with virions and bursts, resulting in cell death.

Steps in Lytic Infection

  • Attachment
  • Penetration
  • Uncoating
  • Biosynthesis
  • Maturation
  • Release

Virion Attachment

  • Virus binds to specific receptors on the host cell (viral tropism).
  • Some require co-receptors for successful attachment.

Virion Penetration

  • Adhesion of virus to host receptors.
  • Engulfment into vesicle.
  • Viral RNA is released from vesicle.

Virion Uncoating

  • Uncoating: removal of the capsid;
    • at plasma membrane
    • in the cytoplasm
    • at the nuclear membrane

Virion Biosynthesis

  • Reverse transcriptase makes a DNA copy of the RNA, then uses the newly made DNA as a template to make a complementary DNA strand.
  • Integration of DNA copy into host chromosome.
  • The integrated DNA is now called a provirus

Virion Maturation

  • Involves moving newly made virions to specific sites in the cell for:
    • Intracellular trafficking
    • Assembly

Virion Assembly

  • Most important part is the placement of the viral genome inside the capsid.
  • Virion is assembled while the viral genome is being synthesized.
  • Viral genome is inserted into already-formed capsids.

Virion Release

  • New virions can be released from cells in two ways:
    • Lysis (non-enveloped viruses)
    • Budding (enveloped viruses)

Lysogenic Infection

  • Viral genome becomes incorporated into host cell’s DNA.
  • Remains for a long period of time.
  • Host cell lives.
  • Also known as LATENT infections.
    • HIV
    • Hepatitis B and C
    • HPV

Lysogenic Process

  • Phage attaches to host cell and injects DNA.
  • Phage DNA circularizes and enters lytic cycle or lysogenic cycle.
  • Prophage (integrated phage DNA) replicates along with the bacterial chromosome during cell division.
  • Occasionally, the prophage may excise from the bacterial chromosome by another recombination event, initiating a lytic cycle.

Viral Infection Patterns

  • Acute infection: Virions released from host cell over a short period, followed by clearance.
  • Latent infection: After initial infection, virus enters a dormant phase; can reactivate later.
  • Persistent infection: Continuous release of virions over a long period.

Antigenic Shift

  • Process of viral antigenic variation caused by the reassortment of genes.
  • Shuffling of the viral genome leads to major changes in viral proteins.
  • Host immune system does not recognize the changed proteins.

Antigenic Drift

  • Process of viral antigenic variation that results from mutations.
  • Epitopes are not recognized by cytotoxic T cells.

Vaccines

  • Live attenuated: intact viral particles that have been mutated and selected for poor infectivity e.g. MMR (measles, mumps, and rubella) and oral poliovirus (OPV)
  • Inactivated (“killed”): composed of a “dead” or non-infectious virus via chemical or physical treatment e.g. inactive poliovirus (IPV)
  • Sub-unit: composed of immunogenic parts of the virus via genetic engineering and recombinant DNA technology e.g. Hepatitis B

Prions

  • A misfolded protein is the active component of the infectious agent.
  • The propagation of the disease and its unique features depends on the self-replication of the infectious folding of the prion protein.

Prion Timeline

  • Highlights key events in prion research, from accidental transmission of scrapie in sheep (1937) to in vitro generation of infectious material from recombinant PrP (2010).