Acellular Biological Entities: Viruses, Viroids, & Prions (Outline)

• Acellular entities as infectious agents of animal and plant diseases • Structure and functional properties. • Viral structural components: genome (DNA or RNA), capsid, nucleocapsid, and envelope. Naked and enveloped viruses • Parasitic nature of viruses – Life cycle of bacteriophages and relationship to human disease – Host-cell specificity: common human diseases – Life cycle of animal viruses and association with susceptibility to infection. – Human genetic variability in susceptibility to viral infections • Life cycle of the Ebola virus • Life cycle of a retrovirus such as HIV • Role of ancient and current retroviruses: – In shaping the human genome; addition of genetic variability – as selective pressure for human genetic variability Acellular Disease-causing biological entities (Health Connection)

Simple infectious agents Virus- genetic material in transit from one host cell to the next Viroid- Circular naked RNA Prion- misfolded infectious proteins Viroids and Prions: The Simplest Infectious Agents • Viroids are circular RNA molecules that infect plants and disrupt their growth- Cadang-Cadang of coconut trees

• Prions are slow-acting, virtually indestructible infectious proteins that cause brain diseases in mammals Prion diseases • Prions are mis-folded infectious proteins, lack nucleic acids

• Prions cause disease by converting normal proteins into the prion version

• Diseases caused by prions affect the nervous system Scrapie in sheep Mad cow disease Kuru in humans Creutzfeldt-Jakob Disease (CJD) in humans Fatal Familial Insomnia (FFI)

The Truth Will Out: Is vCJD Caused by BSE? http://ffh.films.com/PreviewClip.aspx?id=5955 (5 mins)

Acellular Disease-causing biological entities (Health Connection) Virus • Childhood diseases • Age-independent disease • Emerging diseases – Discovery Channel Video Clip (Textbook site) Viroid • Plant diseases

Prion • Scarpie • Mad Cow disease • Kuru- Fore tribe of Papua New Guinea Viruses are genes packaged in protein – Biological non-living entities – Have no cytoplasm – Cannot self-replicate – Cannot metabolize – Genetic material either DNA or RNA never both Viruses

• To replicate they need to infect a living cell • Every living cells has one or more viruses that can infect it, specifically.

Viral Shapes Naked Enveloped Complex

RNA Membranous Head DNA envelope RNA Capsomere DNA Capsid Tail sheath Capsomere Tail of capsid fiber Glycoprotein Glycoproteins 18  250 nm 70–90 nm (diameter) 80–200 nm (diameter) 80  225 nm

20 nm 50 nm 50 nm 50 nm (a) Tobacco mosaic (b) Adenoviruses (c) Influenza viruses (d) Bacteriophage T4 virus Viral Structures

• Virion: an individual viral particle • Capsid: protein coat surrounding the nucleic acid Capsid made of individual protein subunits (capsomeres) gives the virion its shape

• Nucleocapsid- nucleic acid and protein capsid

Basis of Host-Range of Viruses

• Host range is determined by “lock-and-key” fit between virus surface and cellular receptors on host cell

• Most viruses infect only specific types of cells in one host Narrow host range with tissue specificity – cold viruses: upper respiratory tract cells. – HIV, AIDS virus: a certain white blood cell.

• Some have a broad host-range infecting multiple species – rabies

Viral genomes are made of either DNA or RNA – Flu viruses are RNA – Genital warts virus (HPV) and Herpes virus are DNA viruses http://www.cdc.gov/STD/HPV/STDFact-HPV.htm Membranous envelope

RN A Protein coat

Glycoprotein spike

Influenza HPV Plant viruses are serious agricultural pests – Most plant viruses have RNA genomes Enter their hosts via wounds in the plant’s outer layers

Protein RNA Emerging viruses threaten human health

Colorized TEM × 50,000 Colorized Colorized TEM × 370,000 Colorized

Figure 10.20A, B

Ebola Virus (RNA) SARS Virus (RNA) Bacteriophage Life Cycles

Daughter cell with prophage Phage The phage injects its DNA. DNA Cell divisions produce population of Phage DNA Phage bacteria infected circularizes. with the prophage. Bacterial chromosome Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle.

Lytic cycle Lysogenic cycle The bacterium reproduces, The cell lyses, releasing phages. copying the prophage and transmitting it to daughter cells. Lytic cycle or Lysogenic cycle Prophage is induced is entered

New phage DNA and proteins Phage DNA integrates into are synthesized and the bacterial chromosome, assembled into phages. becoming a prophage. Bacteriophage Life Cycles Lytic Cycle Lysogenic Cycle

• Attachment • Attachment • Entry of DNA • Entry of DNA • Degradation of host DNA • No degradation of host • Replication of nucleic DNA acid and synthesis of • Integration of nucleic into viral proteins bacterial genome • Packaging/Assembly of • Prophage: an integrated phage particles (DNA phage and proteins) • Exit to lytic cycle induced • Release by cell lysis by chemicals and high energy radiation

Prophage-mediated Diseases • One of many reasons for why bacteria cause disease is the production of a toxic protein.

• Some proviral genes code for toxic proteins. • Examples: o Diphtheria o Botulism o Scarlet fever o E. coli food poisoning Animal Virus Life Cycle

• Attachment • Entry ? • Uncoating of virion separate protein from NA • Replication of nucleic acid and synthesis of viral proteins • Maturation of virions (assembly of NA and proteins) • Release: cell lysis or budding http://www.youtube.com/watch?v=cE 0qdqoBFa8 The Ebola virus – An enveloped RNA (- strand) Entry and exit – http://www.youtube.com/watch?v=57P6MuM3_F8

Pathogenesis – http://www.openculture.com/2014/11/the-ebola-virus- explained-with-animated-video.html

Transmission

Links http://www.cdc.gov/vhf/ebola/transmission/index.html?s_cid= cs_284 http://www.who.int/mediacentre/factsheets/fs103/en/

The AIDS virus – HIV is an RNA retrovirus – It makes DNA using RNA template – Inside a cell, HIV uses its RNA as a template to make a DNA copy of itself, which integrates into the host genome. http://www.susanahalpine.com/anim/KubyHTML/HIV.htm

Envelope

Glycoprotein

Protein coat

RNA (two identical strands)

Reverse transcriptase Viral DNA in the Human Genome About 8% of our genome is derived from RNA viruses called retroviruses - This is evidence of past infection - Sequences tend to increase over time

Figure 11.11 Roles of human endogenous retroviruses Endogenous retroviruses • Placenta formation • Large Brain development • Powerful emotions

Explorer: The virus hunters (DVD) Natgeotv.vom http://channel.nationalgeographic.com/series/expl orer/3828/Overview#tab-Videos/06253_00 The Virus Hunters (DVD)

• Retroviruses in human genomes (first 12:30 mins)

Role for Viruses in shaping the Human Genome • Past retroviral infection in a primate ancestor – Insertion of sequences – New proteins or protein domains for host that maybe beneficial and influence behavior

• Present retroviral infections add to the genetic variability of the human populations The Virus Hunters (DVD)

• Role of ancient retroviruses in major evolutionary steps (12:30- 15:30 mins)

The Virus Hunters (DVD)

• Role of integrated viruses in complex emotions and behavior (~40:30 to 46:20 mins)