General Properties of Viruses

GENERAL PROPERTIES OF VIRUSES [email protected]  General Characteristics of viruses ✓ They are unique, smallest heterogeneous infectious agents with sizes ranging from 20-300nm in general ✓ They are non-cellular structures that have a nucleic acid core containing DNA or RNA ✓ Viruse...

GENERAL PROPERTIES OF VIRUSES [email protected]  General Characteristics of viruses ✓ They are unique, smallest heterogeneous infectious agents with sizes ranging from 20-300nm in general ✓ They are non-cellular structures that have a nucleic acid core containing DNA or RNA ✓ Viruses contain a protein coat called the capsid (for protection, attachment, and entry) ✓ Viruses are obligate intracellular parasites; grow only in living cells ✓ They lack ribosomes and enzymes needed for metabolism ✓ They use the raw materials and enzymes of the host cell to be able to reproduce through processes of complex biosynthesis 2 General characteristics ✓ They are not susceptible to antibiotics (antibiotics target cellular structures eg., cell wall which viruses lack, viruses do not replicate on their own and do not perform any metabolic activities on their own) ✓ Viruses are susceptible to antimicrobial chemical agents e.g. chlorine, alcohol, formalin, etc ✓ Viruses can infect unicellular organisms such as mycoplasmas, bacteria, and algae ✓ They can also infect higher plants and animals including insects. 3 General characteristics ✓ Major viral groups are - Plant viruses - Insect viruses - Viruses of bacteria (bacteriophage) - Viruses of vertebrates (animal viruses) 4 Virus structure ✓ A virion which is an infectious particle has at least two components: - Molecules of either DNA or RNA ( ie. the genome) - An outer symmetrical protein shell known as the capsid ✓ The nucleic acid and the capsid is referred to as the nucleocapsid ✓ Some viruses apart from the nucleocapsid may have an extra membrane called the envelope ✓ Viruses made up of nucleocapsid alone are referred to as naked viruses ( eg., Human Papillomavirus, Poliovirus) ✓ Viruses with the envelope are called enveloped viruses (eg., SARS-COV-2, Ebola, HIV, Hepatitis C) 5  Virus Structure Virus strcuture Bacterial structure 6 Chemical composition of viruses ✓ Viral nucleic acid ✓ Viral protein - Capsid - Enzymes ✓ Viral lipids ✓ Viral glycoproteins 7 Nucleic Acid ✓ The viral nucleic acid constitutes the genome (complete set of genetic material) which carries the genetic information necessary for replication ✓ The viral nucleic acid may be - Single or double-stranded - Circular or linear - Segmented or non-segmented - Positive or negative polarity ✓ Each family of viruses possesses a nucleic acid characteristic of that group ✓ We can analyze the sequence or composition of nucleotides by using restriction nucleases 8 Nucleic acid ✓ All the animal RNA viruses are single-stranded (eg., poliovirus, rhinovirus, SARS-CoV, MERS-CoV, and SARS-CoV-2 (COVID-19) except the REO (rotavirus) viruses. ✓ All the animal DNA viruses are double-stranded (Eg. Human papillomavirus, herpes simplex virus, Poxviridae (variola virus)) except the PARVOVIRUSES ( eg., hepatitis B virus (HBV) 9 Viral Protein - Capsid ✓ The capsid is composed of individual polypeptides – coded by the virus ✓ The number and appearance of capsomers (protein subunits of the capsid) are characteristic of a virus and important in its identification The capsid performs four functions ✓ It protects the nucleic acid from damage in the external environment ✓ It facilitates attachment to susceptible cells ✓ It confers structural symmetry on the virion ✓ It confers antigenicity (the ability of the virus/antigen to specifically bind to components of the immune system)) 10 ✓ Viral capsids (coats) are made of individual protein subunits ✓ Individual subunits are called capsomeres CAPSOMERES 11 Viral protein-Enzymes ✓ Polymerase ✓ Integrase ✓ Reverse transcriptase Viral Lipids-Envelope ✓ The lipids are part of the envelope and are coded for by the host cell 12 Viral Glycoprotein ✓ Viral envelope contains glycoproteins in the form of projections on the envelope - Neuraminidase (cleaves sialic acid from glycoproteins to release new viral particles) and haemagglutinin (facilitate initial attachment of virus to host cells by binding to sialic acid) - They are virus coded 13 Viral Envelope ✓ The viral envelope is acquired by the virus during the final stages of replication ✓ The envelope consists of a bilayer membrane containing glycoprotein and lipid 14 Viral Envelope ✓ Functions are similar to capsid in naked virions: - It protects nucleic acid from damage - It facilitates attachment - It confers structural symmetry - It confers antigenicity 15 General Morphology of the Virion ✓ Compared to most micro-organisms the virus particle is the smallest - Measured in nanometers (10-9 meters = nm) ✓ Viruses range in size from about 20 to 25nm for parvoviruses and picornaviruses to 200-300nm for poxviruses ✓ Most plant viruses are rod-shaped whilst bacterial viruses show a more elaborate, tailed structure 16 17 Virion Morphology ✓ The shapes of most animal viruses are frequently referred to in colloquial terms e.g. spheres, rods, bullet or brick-shaped. ✓ In reality they are complex structures of precise geometric symmetry ✓ The shape of the virus particle is determined by the arrangements of the repeating subunit that form the capsid ✓ Precise geometric symmetries are - Icosahedron - Helix (worm-like or coiled configuration) - Complex (irregular configuration) 18 Icosahedron ✓ The shape of a regular icosahedron has 20 faces each of which is an equilateral triangle. ✓ The viruses have their nucleic acid packaged inside the capsid - Capsid can be naked or enveloped 19 20 Helical Viruses ✓ In many RNA viruses, the viral nucleic acid is closely associated with the capsid forming a coil-shaped, helical structure ✓ A viral envelope always surrounds helical animal viruses 21 causes influenza 22 Complex viruses ✓ Viruses that do not fit into any of the two symmetries due to the complexity of the virion are described as complex. Eg., HIV, Poxvirus 23 Virion Morphology ✓ The virus can be grouped into five categories based on their morphology and nucleocapsid symmetry - Naked icosahedral viruses - Enveloped icosahedral viruses - Naked helical viruses - Enveloped helical viruses - Complex viruses 24 Reaction to chemical and physical agents Heat and cold ✓ Different viruses show variable stability to heat and cold ✓ Icosahedral naked viruses tend to be stable at 37°C losing little infectivity after several hours ✓ Enveloped viruses are much more heat-labile; rapidly dropping in titre at 37°C 25 Effect of heat and cold on viruses ✓ Viral infectivity is generally destroyed by heating at 50°- 60°C for 30min ✓ Viruses can be preserved by storage at sub-zero temperatures - Some may withstand lyophilization and can be preserved in the dry state at 4°C or even at RT ✓ Enveloped viruses tend to lose infectivity after prolonged storage even at -90°C and are very sensitive to freezing and thawing 26 Stabilization of viruses by salts ✓ Many viruses can be stabilized by salts in concentration of mol/L - Some viruses are not inactivated in the presence of these salts - Mechanisms of this protection are unknown Eg., MgCl2 stabilizes Picornaviruses - MgSO4 stabilizes Myxoviruses - Na2SO4 stabilizes herpes viruses ✓ The stability of viruses is important in the preparation of vaccines ✓ Salts are added to vaccines to stabilize the preparation 27 Stabilization of viruses by salts-pH ✓ Viruses are usually stable between pH values of 5 and 9. ✓ Some viruses are resistant to acidic conditions e.g. enteroviruses ✓ Extreme alkaline conditions destroy all viruses 28 Photodynamic inactivation and reaction ✓ Viruses can be penetrated to varying degrees by vital dyes e.g. neutral red, toluidine blue, and proflavine ✓ Dyes bind to nucleic acid making it susceptible to inactivation by visible light ✓ Ultraviolet, x-ray, and high-energy particles inactivate viruses - They are used in sterilization of plastics, benches - Dose varies for different viruses 29 Ether and Detergents ✓ Ether, like other lipid solvents acts on the lipid in the viral envelope ✓ Non-ionic detergents solubilize lipid constituents of viral membrane ✓ Anionic detergents solubilize viral envelopes and disrupt capsids into separate polypeptides 30 Formaldehyde ✓ Formaldehyde destroys viral infectivity by reacting with nucleic acid ✓ Single-stranded genome is much more readily inactivated than double-stranded genome. ✓ Frequently used in the production of inactivated viral vaccines 31 Antibiotics & antimicrobial agents ✓ Antibiotics and sulphonamides have no effect on viruses ✓ Antimicrobial agents e.g. chlorine at high concentrations are required to kill viruses ✓ Alcohols such as isopropanol and ethanol in their pure forms are relatively ineffective against certain viruses e.g. picornaviruses NB: 50-70% ethanol more effective 32 Mode of transmission ✓ The route of transmission depends on the source and the body route to the target tissue. ✓ Naked viruses can withstand drying, the effects of detergents, and extreme pH and temperature. - The respiratory and fecal-oral routes generally transmit them. - They can also be acquired from contaminated objects ✓ Enveloped viruses are comparatively fragile - They require an intact envelope for infectivity NB: They must remain wet and are spread through: - respiratory droplets, blood, mucus, saliva, or semen - injection - Organ transplantation 33 Susceptibility to transmission ✓ Infants, children, and elderly are susceptible to different viruses ✓ The competence of a person’s immune response and his/her immune history determine how quickly and effectively the infection is resolved and can also determine the severity of symptoms 34  Some viruses of medical importance Flaviviruses (yellow fever virus) Ebola Measles Rubella Polio Mumps SARS COV-2 MERS COV Varicella Zoster Virus 35 Varicella Zoster Virus (VZV) Virus Characteristics It belongs to the family of Herpesvirus (human herpesvirus 3) It is a double-stranded DNA with an approximate size of 150-200 nm in diameter It has a lipid envelope derived from the host cell membrane Structure It has an Icosahedral capsid enclosing the viral DNA The Tegument contains viral proteins The Envelope Contains glycoproteins essential for virus entry into the host cell 36 37 Diseases Caused Primary Infection: Varicella (chickenpox), characterized by a vesicular rash, fever, and malaise Reactivation Herpes zoster (shingles), characterized by a painful, unilateral vesicular rash along a dermatome (an area of skin that is mainly supplied by a single spinal nerve) Mode of Attachment Glycoproteins on the viral envelope interact with host cell surface receptors, facilitating viral entry Fusion with host cell membrane allows entry of the viral capsid into the host cell cytoplasm 38 Diagnosis Clinical Presentation ✓ Characteristic rash and symptoms Laboratory Tests PCR-Detection of VZV DNA in lesions, blood, or cerebrospinal fluid DFA (Direct Fluorescent Antibody)-Detection of VZV antigens in skin lesions Serology-Detection of VZV-specific IgM and IgG antibodies 39 Control and Treatment Vaccination Varicella Vaccine ✓ Live attenuated vaccine for prevention of chickenpox ✓ Zoster Vaccine-Recombinant vaccine for prevention of shingles in older adults Antiviral Medications Acyclovir, Valacyclovir, Famciclovir: Used to treat and reduce the severity of both chickenpox and shingles 40 Influenza virus ✓ Causes acute respiratory infection Transmission -Spreads easily through coughs or sneezes Symptoms ✓ Fever, cough, sore throat, body aches, fatigue, headache, muscle and joint pain, severe malaise, runny nose 41 High-Risk Groups ✓ Pregnant women ✓ Children under 5 years ✓ Older adults ✓ Individuals with chronic conditions or immunosuppression ✓ Health and care workers Transmission ✓ Droplets from coughs/sneezes ✓ contaminated hands Diagnosis ✓ Clinical diagnosis is based on symptoms 42 ✓ Laboratory Tests - PCR (high sensitivity) - Rapid diagnostic tests (lower sensitivity) - Treatment - Rest, take enough fluids, and symptom relief. - Antivirals-For high-risk individuals or severe cases. Prevention ✓ Cover mouth/nose when coughing ✓ wash hands regularly 43 44  SARS-COV-2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA virus of the genus Betacoronavirus Other members of the genus include MERS-COV, SARS-COV, and human coronavirus (HCoV)-OC43, HCoV-HKU1. The coronavirus virion is made up of the nucleocapsid (N), membrane (M), envelope (E) and spike (S) proteins, which are structural proteins. The SARS-COV-2 attaches itself to the host and enters the host by the help of the S glycoprotein 45 Mode of Transmission Direct Transmission ✓ Respiratory droplets from coughs, sneezes, and talking Indirect Transmission ✓ Contact with contaminated surfaces followed by touching the face Aerosol Transmission ✓ Small particles that remain airborne for longer periods Mode of Attachment ✓ Receptor Binding- S protein binds to the ACE2 receptor on host cells ✓ Fusion-Viral membrane fuses with the host cell membrane, allowing entry 46 Target Tissue ✓ Primary Target -Respiratory tract, particularly the alveolar epithelial cells -Other Targets-Gastrointestinal tract, endothelial cells Mechanism of Infection ✓ Entry-binding of S protein to ACE2 and fusion with the host cell membrane ✓ Replication-Viral RNA is released, translated, and replicated in the host cell cytoplasm ✓ Assembly-New viral particles are assembled in the host cell ✓ Release-Virions are released from the host cell, often causing cell damage and inflammation 47 48 Prevention Vaccination ✓ mRNA vaccines (e.g., Pfizer-BioNTech, Moderna) ✓ viral vector vaccines (e.g., AstraZeneca, Johnson & Johnson) ✓ inactivated virus vaccines (e.g., Sinopharm, Sinovac) Non-Pharmaceutical Interventions ✓ Wearing nose mask, hand hygiene, physical distancing, ventilation of indoor spaces 49  HOMEWORK TWO Discuss the key characteristics, mode of transmission, diseases they cause, pathogenesis, and prevention of the following: Polio virus HIV 50