Failure to Control

• • Viruses are genome surrounded by a protective protein coat, which are infectious & aims to get genetic material inside a host cell to undergo replication.
• • A basic virion consists of: genome (i.e. DNA or RNA), surrounded by nucleocapsid, which are transferred to target cell; matrix proteins, which gives rigidity to virion; envelope, which are flexible & pleomorphic, made of host cell membrane lipids (i.e. can be intracellular organelle membrane) modified to contain virus proteins; & surface protein/glycoprotein, which interacts with & attaches to host cell.
• • The unique features of viruses compared to other microbial pathogens are that: viruses are very small, so cannot be visualised by light microscopy & detail information can only be obtained from transmission electron microscopy (i.e. bombarding virus with electrons), Cryo-EM & computer reconstruction from X-ray crystallography data; & viruses are classified by Baltimore classification, based on strategy employed to replicate genetic material/form mRNA for new infectious viral protein transcription & translation.
• • Structures between different viruses are diverse by: different genetic material, where virions can be RNA/DNA, single/double stranded & linear/circular/segmented; capsid symmetry (i.e. icosahedral/helical capsid) from capsid proteins assembling symmetrically around nucleic acid to protect genome against breakdown by nucleases; & multiple-shelled capsids around some capsids (i.e. have inner & outer capsids), so virion becomes hardy as double capsids provide protection under hostile environments.
• • Virion can have icosahedral capsid, composed of capsomers in 2-,3- & 5-folds. This symmetry is energy efficient packaging of viral proteins & may or may not be surrounded by an envelope.
  • Virion can have helical capsid, composed of capsid protein forming repeating units of rod-shaped coat around nucleic acid as single protomer in spiral/helical arrangement. This symmetry has no helical DNA virus, & helical RNA is always enclosed in envelope.
• • The stages of replication cycles of viruses involve: attachment, evolved viruses utilise/attach to normal function, host cell receptors; penetration, direct fusion with plasma membrane (for enveloped virion) or endocytosis then endosomal escape (for both virion); uncoating, capsid sheds so virus with RNA use cytoplasm & DNA use nucleus; replication, virus families have different ways to form viral mRNA & proteins; assembly, enveloped virion trafficked to/glycosylated in ER & Golgi, non-enveloped build up in cell; release, enveloped via budding from cell surface, non-enveloped via cell lysis.
• • Different viruses replicate & interact with host cells diversely by: DNA viruses using similar strategy as eukaryotic replication; & RNA viruses, using different strategies involving acquiring its own RNA-dependent RNA polymerase (RdRp), since host cells don't have it.
• • The principles in which viruses replicate involve to replicate its genome & to encode new copies of structural & non-structural protein, which will be assembled into new virions to spread in host.
• • Poliovirus replicates by: (+) strand of poliovirus RNA (i.e. basically mRNA) translating polyprotein straightaway; polyprotein cleaved by autocleavage process at specific sites, forming structural coat proteins, proteases (i.e. allow further cleavage for mature proteins) & RNA polymerase (RdRp); mature RdRp synthesis complementary copy of original (+) mRNA ;RdRp uses this (-) strand as template to replicate more (+) strands; new copies being packaged into newly synthesised virion.
• • The general principles of viral pathogenesis to cause infection in host are: gaining entry to body; multiplying & spreading locally or systemically, where cause of infection is determined by immune response after initial acute infection; & targeting appropriate organs.
• • The general principles of viral pathogenesis to be maintained in nature are: shedding into the environment; being taken up by arthropod vectors/needle; & being passed congenitally.
• • Viruses enter within human bodies by: conjunctiva (eyes) or mouth/nose; tracts, such as respiratory, alimentary & urogenital; skin & anus, where most viruses enter through epithelial cells of mucosa since epidermis of skin, covered by dying cells with keratin, is hostile for viruses; & capillary, through arthropods (i.e. mosquitoes), where virus is transmitted by blood.
• • The difference between localised & systemically spread infections is that: localised refers to virus infections confined to organ of entry; & systemic refers to virus infection involving many organs, due travelling from initial to other organs.
• • Viruses enter through respiratory tract & spread within human bodies by: being acquired by aerosol inhalation or mechanical transmissions of infected nasal secretions (i.e. rubbing nose); viruses attaching to specific epithelial cells receptors, so can remain localised (e.g. rhinovirus) or spread further (e.g. measles); & viruses exploiting temperature gradient (i.e. 33 degrees in nose & 37 degrees in lungs), a protective mechanism in tract, to give itself replicative advantage.
• • Viruses enter through alimentary tract & spread within human bodies by acquiring through ingestion via swallowing or infected oropharynx, to be carried elsewhere. Examples of viral infections that enter via alimentary tract are: herpes simplex virus 1 cold sores, acquired by direct contact of infected saliva with damaged skin or mouth & remains localised; & Epstein-Barr virus infectious mononucleosis, acquired by direct contact of infected saliva with oropharynx & disease is manifested elsewhere.
• • Disease symptoms are induced by different viral infections by different mechanisms of spread in the body, such as viremia, spread of virus through bloodstream inducing disseminated infection (i.e. spread beyond primary site) & systemic infection(i.e. many organs infected).
• • Viremia with viruses free in plasma, have primary & secondary phases produced by infected vascular endothelium, & released in large amounts by large organs. Where hosts have developing antibody responses to neutralise virus, such as macrophages to remove viruses, so virus is short-lived (e.g. arboviruses).
  • Viremia with cell-associated viruses affect cells of the immune system (i.e. leukocytes & platelets). Where host initiates cytotoxic T lymphocyte (CTL) attacks to eliminate virus, but virus genome can become latent to avoid attack, so virus lasts longer (e.g. HIV spread in T cells).
• • The different phases of systemic spread of disease via viremia occur by: passive phase, with viruses in blood from initial acute infection at route of entry (e.g. needles) but no replication; primary viremia (i.e. smaller surge than passive), with first emergence of virus in blood after it escapes endothelium & begins replication in large organs (e.g. liver, spleen); secondary viremia (i.e. largest surge), with amplification of virus due to completed replication in large organs, increasing the change of virus targeting exits to body & accumulate/present symptoms for disseminated infection.
• • The different outcomes of infection include: fatal outcome, high mortality rate from viral diseases where humans are not the natural hosts; full recovery outcome, viral disease completely cleared by host immune system (e.g. influenza); recovery but permanent damage outcome, viruses cleared but left with symptoms (e.g. poliomyelitis, damage to NS for paralysis); & persistent infection outcome, viruses not cleared & can resurface to cause disease (i.e. latent infection).
• • The different outcomes of infection occur by: viral damage to tissues & organs, as viral replication can cause loss of function in cells, causing cell damage & death; & consequences from immune response, such as immunopathology (i.e. inflammation, fever, enlarged lymph nodes) & immunosuppression (i.e. viruses grow in cells of immune system), causing "cytokine storm" which results in organ damage (i.e. liver, kidney) to induce hypoxia, resulting in host death.
• • The different outcomes of infection are impactful because it suggests that viruses are constantly evolving & are highly prone to replicative errors, due to no proof-reading mechanism, so can evade immune responses made for them. So viruses can gain selective advantage (as well as being killed, disadvantaged or having no effect) by genome changes from mutations or recombination (i.e. exchange of DNA nucleic sequences) & reassortment (i.e. swapping viral segments in RNA), such as increased growth & immune escape.
• • Anthrax is caused by Bacillus anthracis, a Gram-positive, aerobic, spore-forming bacterium.
  • Bacterium evades immune system by: capsule (i.e. encoded by first plasmid), inhibiting phagocytosis; & exotoxin (i.e. encoded by second plasmid), inhibits transcription factors that regulate innate immune response & binds to/kills host macrophage by forming membrane pores.
  • So it is fatal.
• • Tetanus is caused by Clostridium tetani, a Gram-positive, spore-forming, rod bacterium.
  • Bacterium causes symptoms of: uncontrolled stimulation of skeletal muscle, by spore germination secreting neurotoxin (i.e. tetanospasmin) that cleaves synaptic vesicle membrane proteins; & tissue destruction, by secreting toxin (i.e. tetanolysin).
  • So it is fatal.
• • Gas gangrene is caused by Clostridium perfringens, a Gram-positive, spore-forming rod bacterium, found as a part of normal human intestinal flora.
  • Bacterium causes lasting damage when transmitted to a different/unnatural tissue in body by: tissue destruction, releases enzymes that destroy collagen & tissue proteins; secreted alpha toxins, breaks down muscle tissues via disrupting cell membrane & causing cell lysis; & gas production, causing gas (mainly H) accumulation from carbohydrate fermentation.
  • So it is a long-term pathology.
• • Latent infections are viral infections that are not completely cleared and become latent/hidden in host bodies. Infection can re-emerge again in a localised pattern with different manifestation.
  • An example of this is varicella-zoster virus (i.e. Herpesviridae), where varicella/chickenpox re-emerges as zoster/shingles, when host is distressed.
• • Bacterial diseases can cause reinfection by different serotypes of capsules protecting bacteria through evading the immune system responses. This is because of antigenic variation, a gene shuffling event that changes the surface antigen of bacteria, so the new antigenic variant is no longer recognised by host's current antibodies.
• • Viral diseases can cause reinfection by evolving through mutations, recombination & reassortment of genome, to avoid immune responses made for them.
• • Evolutionary mechanisms of viruses work together to cause reinfection by: antigenic shift, a big evolutionary change in viral genetics via reassortment, producing new novel viruses that can cause worldwide pandemic; & antigenic drift, accumulation of mutations (i.e. RNA copying errors) & recombination in antigen binding sites of viral hemagglutinin (HA), producing new seasonal epidemic strains from selection pressure of neutralising antibodies.