Week 3

• Viruses are almost all too small to be seen in the light microscope, which can only resolve down to approximately half the wavelength of the light used (approximately 200 nm).
• Theories of the origin of viruses include endosymbiosis, panspermia, and exogenesis.
• The main drivers of virus evolution are mutation, recombination, and gene transfer.
• Most meaningful mutations occur in the HA1 protein.
• Mechanisms of HIV evolution include reverse transcription, error catastrophe, and recombination.
• Clinical features of influenza include sudden onset of symptoms that persist for 7+ days, with an incubation period of 1 - 4 days, average 2 days.
• Antigenic shift is a phylogenic evolution that accounts for the emergence of new strains of virus, with immunologically distinct, novel H/N combinations.
• Genetic reassortment between circulating human and animal strains is responsible for shifts, with a segmented genome facilitating reassortment.
• Antigenic drift refers to minor changes in the antigenic character of the virus, with a mutation rate highest for type A, lowest for type C.
• Point mutation of Hemagglutinin and Neuraminidase gene is a method of antigenic drift.
• Mechanisms of Influenza evolution include mutation, recombination, and gene transfer.
• The Infectious Cycle of Coronaviruses involves attachment and entry, translation, genome replication, assembly, and release.
• Viruses can be placed in one of the seven groups according to the Baltimore Classification System: dsDNA viruses (e.g Adenoviruses, Herpesviruses, Poxviruses), ssDNA viruses (+)sense DNA (e.g Parvoviruses), dsRNA viruses (e.g Reoviruses), (+) ssRNA viruses (+)sense RNA (e.g Picornaviruses, Togaviruses, SARS - CoV ), (-) ssRNA viruses (-)sense RNA (e.g Orthomyxoviruses, Rhabdoviruses, Flu), and ssRNA - RT viruses (+)sense RNA with DNA intermediate in life - cycle (e.g Retroviruses).
• By convention, mRNA is defined as a positive (+) strand because it is the template for protein synthesis.
• Only influenza A viruses are further classified by subtype based on the two main surface glycoproteins, HA and NA.
• After export of viral mRNAs from the nucleus to the cytoplasm, viral proteins are expressed and the newly synthesized RdRp constituents and NPs are imported into the nucleus, facilitating vRNA replication and vRNP formation.
• Influenza A is an enveloped virus with a genome made up of negative sense, single-stranded, segmented RNA.
• Influenza A belongs to the family of Orthomyxoviridae.
• The virus binds to hemagglutinin (HA) mediated receptor binding by endocytosis and membrane fusion, releasing internal genetic contents into the cytoplasm.
• Progeny vRNPs are then transported into the cytoplasm, assemble, and bud at the plasma membrane.
• Influenza viruses infect 15 - 20% of the world’s population annually, resulting in 3 - 5 million severe cases and 250 - 500,000 deaths/year.
• The three types of influenza viruses are A, B, and C.
• Progeny virions are released from the host cell surface via viral neuraminidase (NA) mediated receptor destroying.
• Hepadnaviruses are dsDNA - RT viruses.
• The 'regression' hypothesis suggests that viruses emerged through the degeneration of cells (probably bacteria) that then assumed a parasitic lifestyle.
• The 'escaped genes' hypothesis proposes that cellular genes acquired the ability for 'independent' replication and spread.
• Retroviruses are dsDNA - RT viruses.
• Orthomyxoviruses, Rhabdoviruses, Flu) are ssRNA - RT viruses.
• Viruses co-evolved with cells from the origin of life.
• Viruses are ancestral to cells and have RNA molecules with enzymatic activity and the ability for self-replication.
• Picornaviruses, Togaviruses, SARS - CoV) are ssRNA viruses.
• Viruses evolved on multiple, independent occasions in different cellular organisms.
• RNA and DNA strands that are complementary to the (+) strand are, of course, called negative ( - ) strands.
• If there is passage through repeated bottlenecks, accumulated mutations approaches the error and fitness plummets.
• Influenza A virus has three types, is envelope, has surface spikes, hemagglutinin protein (HA) (16 types), neuraminidase protein (NA) (9 types), and SS( - ) RNA.
• Influenza Virus diversity is represented by the number of surface spikes, hemagglutinin protein (HA) types, neuraminidase protein (NA) types, single-stranded RNA (SS( - ) RNA), and 8 segmented genes.
• Inaccurate DNA synthesis by reverse transcriptase (RT) which lacks 3’ 5’ exonuclease proofreading to correct errors and HIV-1 RT is also error-prone during DNA synthesis with viral DNA substrates contribute to HIV diversity.
• Viral Quasispecies are genomes indicated by horizontal lines, mutations by different symbols, and the consensus as a single line at the bottom.
• Bottleneck is extreme selective pressure on small populations that results in loss of diversity followed by the accumulation of non-selected mutations.
• Influenza A virus has many subtypes differentiated by HA and NA, named by specific HA and NA subtypes.