Micro bio

• Capsids


  • Formed by ordered arrays of protein subunits
• Lipids


  • Derived from host membranes
• Glycoprotein spike proteins


  • May be studded on capsids (encoded by the virus)
• Capsids


  • May be enclosed in lipid envelopes
• Pox viruses


  • Genome is surrounded by several layers of membrane and proteins
  • Also contain a large number of accessory proteins
  • Virions often contain proteins as well as genomes
• Virion binding and entry into host cells


  1. Virion binds to specific proteins on host cell surface

  2. Bacteriophages: genome is injected into the host cell, leaving the capsid "ghost" behind on the surface
• Phage life cycles


  1. Lytic phages/lytic cycle: infect, reproduce, lyse host cell

  2. Lysogenic (aka temperate) phages: Infect, integrate phage genome into host genome, enter lytic cycle later
• Roles of phages


  • Lytic phages: Drive bacterial evolution by exerting selective pressure, Limit bacterial growth in certain environments
  • Lysogenic phages: Drive bacterial evolution by facilitating exchange of genetic material, Provide many useful tools for genetic engineering and biotechnology
• Animal virus entry into host cells

  1. Usually (but not always) the whole virion enters the host cell

  2. Viral genome may be delivered to the cytoplasm or to the nucleus
• Membrane fusion and viral entry

  1. Interactions between virions and host cell surface proteins or carbohydrates are part of what dictate host range and which cell types are infected

  2. Many viruses infect only a single species and one or a few cell/tissue types

  3. Some viruses have broader ranges

  4. Mutations in viral proteins can allow "jump" from one host to another
• Influenza virion structure and genome


  • RNA genome is loosely contained by a shell of matrix proteins
  • 8 separate RNA genome segments encode proteins
  • RNA segments are coated with proteins
  • Two major envelope proteins: Neuraminidase (NA) and Hemagglutinin (HA)
  • The envelope proteins are the source of flu strain names
• Influenza attachment and host cell entry

  1. The HA envelope protein attaches to a host cell by binding to a sialic acid receptor protein

  2. The virion is taken up by endocytosis

  3. Acidification induces a conformational change

  4. Fusion of envelope and the host membrane

  5. Virion contents are released into the cytoplasm
• Sialic acid variations


  • Human and avian upper respiratory tract cells have different variations of the carbohydrate sialic acid attached to proteins on their surfaces
  • The HA in avian flu binds this
  • The HA in human flu binds this
• Viral genomes


  • DNA viruses can utilize the host replication machinery
  • RNA viruses use an RNA-dependent RNA-polymerase to transcribe their mRNA
  • Retroviruses use a reverse transcriptase to copy their RNA genomes into DNA for insertion in the host chromosome
• Animal virus replication cycles

  1. All animal viruses use host ribosomes to make proteins, Translation occurs in the cytoplasm

  2. Assembly of new virions: Capsid and genome are assembled, May occur in the cytoplasm or nucleus, Envelope proteins are inserted into a membrane (cell membrane or organelle membrane)
• Release of progeny viruses from host cell

  1. Lysis of cell, Most bacteriophages, some animal viruses

  2. Budding: Virus passes through membrane, Membrane lipids surround capsid to form envelope, All enveloped viruses bud from a membrane (either plasma membrane or organelle membrane)
• HIV


  Human immunodeficiency virus
• AIDS


  Acquired immunodeficiency syndrome
• 800,000 deaths from HIV/AIDS in 2018 (WHO)
• HIV/AIDS is the third most deadly single pathogen after SARS-CoV-2 and M. tuberculosis
• 37.9 million people living with HIV in 2018 (WHO)
• Antivirals suppress viral activity but do not cure HIV
• No vaccine for HIV
• How HIV suppresses the immune system

  • Viruses suppress immune system primarily by killing CD4+ T cells, resulting in death from opportunistic infections and cancer
• HIV prevalence


  • Map and data: WHO
• Decline in HIV incidence and mortality over time

  1. Antiretroviral therapy coverage

  2. AIDS-related deaths
• Antiretroviral drugs reversed the trajectory of the AIDS epidemic
• Antiretrovirals prevent AIDS and reduce transmission
• Retrovirus


  Single-stranded RNA genome, gets reverse-transcribed into DNA
• HIV (Retrovirus) Life Cycle


  1. Virion contains RNA genome and reverse transcriptase (RT)

  2. RT makes a DNA copy of the viral genome, which integrates into the host chromosome

  3. Host RNA polymerase transcribes the integrated viral genome

  4. RNA is translated into protein and also packaged into new virions
• HIV infects T cells and other lymphocytes (cells of the immune system)
• Cell surface proteins required for HIV entry

  CD4 and CCR5
• CCR5 mutations confer resistance to HIV infection
• CCR5 Δ32 mutation


  • ~1% of people of northern European decent are homozygous for this mutation
  • CCR5 Δ32 homozygotes are resistant to HIV infection
  • CCR5 Δ32 heterozygotes (~10% or people of northern European decent) may have partial resistance
  • The high frequency of the CCR5 Δ32 allele suggests it has been under positive selection prior to the emergence of HIV
• Cystic fibrosis (CF)


  Genetic defect that affects lung mucus
• Lung mucus in CF patients

  • Thicker lung mucus and less efficient clearance of foreign particles and pathogens
  • Chronic lung infections lead to compromised lung function and death
• Mycobacterium abscessus


  • Causes chronic infections in CF patients
  • Related to the bacterium that causes tuberculosis
  • Intrinsically resistant to most antibiotics
  • Chronic infections treated by multiple drug combinations that often control but don't clear the infection
  • Common cause of death in CF patients
• Phage therapy for a CF patient with M. abscessus infection

  1. Obtain M. abscessus from her infection

  2. Screen mycobacteriophage collection for phages that can infect this M. abscessus strain

  3. Genetically modify lysogenic phages to make them lytic

  4. Treat with a combination of three phages i.v., every 12 hours for >6 months
• Isabelle's infection was not fully cured by phage therapy
• Isabelle's phage cocktail is ineffective against other clinical isolates of M. abscessus