Lecture 23: Viruses

“Sub-microscopic particle (20-300nm) that can infect cells of biological organism” Obligate intracellular parasites: 1. cannot carry out any metabolic pathway 2. Neither grow or respond to environment 3. Cannot reproduce independently

• Extracellular: a. Virion b. Core nucleic acid (DNA or RNA) c. Protein coat: “capsid” d. Envelope (some virions): phospholipid membrane; allowing interaction with target cells • Intracellular: a. Virus exists as the nucleic acid (episomal or integrated)

• Most viruses infect a particular type of cell. E.g., HIV & CD4 positive cells on surface of T cells • Specific affinity of viral surface proteins/glycoproteins to complementary proteins/glycoproteins on host surface • Few are “generalists” - E.g., Rabies

• Attachment - chemical attraction • Entry - direct penetration (“poliovirus”), membrane fusion (“measles and mumps”), phagocytosis (“herpes”), uncoating of capsid may be involved • Synthesis - different viruses (ss/ds DNA/RNA) have different strategies • Assembly - DNA viruses assembled in nucleus, RNA viruses in cytoplasm • Release - enveloped viruses released by budding, naked viruses via exocytosis of cell lysis

• Small pox (“poxviridae”) a. middle ages (80% of European population go it) b. 18th century; was introduced to native Americans - up to 3.5 million died c. Edward Jenner showed immunization using mild cowpox d. Eradication possible due to: inexpensive & stable vaccine, specificity to infection, quick+obvious signs of infection (allowed quarantine), lack of carriers, close contact spreading e. CAUSED BY TWO VIRUSES: Variola major & Variola minor 2.

• ALMOST eradicated • ssRNA (acts as mRNA) 3.

• Common cold: Rhinovirus a. as well as coronavirus, reovirus, adenoviruses b. affect epithelial cells of upper respiratory tract c. Gain entry after attach. to intracellular adhesion molecule ICAM-1 d. Triggers inflammatory pathways e. Interleukin-1, 6, 8 responsible 2. Chicken pox: Varicella-Zoster virus HHV-3 (Herpesviridae) a. Enveloped polyhedral capsids b. linear dsDNA c. Enter via respiratory tract d. attach to receptor and fuse envelope to cytoplasmic membrane e. replicate at site, traverse via blood f. Often "latent infection" g. can reactivate to produce shingles • Parvoviridae a. only human pathogens with ssDNA b. B19 - erythema infectiosum; reddening of skin c. No treatment

• Infective agents evolution • Globalisation • Habitat modification

1. Enveloped + ssRNA viruses with reverse transcriptase 2. "Retroviridae" 3. Spike proteins: a. glycoprotein120 (gp120) b. gp41 4. Bind to CD4 receptor

• Genesis of the swine-origin influenza virus A/H1N1 • A merge of Classical swine (H1N1), North American avian (H1N1), human (H3N2), and Eurasian avian-like swine (H1N1) • N = neuraminidase: hydrolyse mucous in lungs • Hemagglutinin protein (H1-16) a. binds to human receptors b. triggers endocytosis c. Binds to sialic acid of target cell d. Acidification inside endosome causes HA conformational change - fusion peptide grabs endosome membrane e. Membranes pulled together • antigenic drift and shift responsible for new strains