Viruses and Human Diseases

Question 1

What is host range / infection

Answer 1

• Host Range: The spectrum of host cells a virus can infect, most viruses infect only specific types of cells in one host, determined by specific host attachment sites and cellular factors
• Bacteriophages: Viruses that infect bacteria
• Infection: The outer surface of virus must chemically interact with specific receptor sites on the surface of cell, combination of attachment / receptor sites leads to an association between host and virus

Question 2

What is transmission and the different types

Answer 2

• Transmission: Direct / indirect contact (fomites) or a vector (animal / arthropod that transmits a pathogen)
• Mechanical transmission: Arthropod carries a viral pathogen on outside of its body and transmits it to a new host by physical contact
• Biological transmission: Arthropod carries the viral pathogen inside its body and transmits it to the new host through biting

Question 3

What are general characteristics of viruses

Answer 3

• Obligatory intracellular parasites that contain a single type of nucleic acid, either DNA or RNA
• Contain a protein coat (sometimes itself enclosed by an envelope of lipids, proteins, and carbohydrates) that surrounds the nucleic acid and often have spikes
• Multiply inside living cells by using the synthesising machinery of the cell, most viruses infect only specific types of cells in one host
• Cause synthesis of specialised structures (viral proteins) that can transfer the viral nucleic acid to other cells (replication / transmission)
• Host range is determined by specific host attachment sites and cellular factors

Question 4

What is a virion

Answer 4

• Complete, fully developed, infectious viral particle composed of nucleic acid and surrounded by a protein coat (protection) outside a host cell

Question 5

Describe the virion structure

Answer 5

• Nucleic Acid: Viral genes are encoded by either DNA or RNA, never both, can be linear or circular
• Capsid: Protein coat that protects nucleic acid, structure of capsid is determined by viral nucleic acid and accounts for most of mass of a virus, made up of protein subunits called capsomere’s
• Envelope: Covers capsid, consists of lipids, proteins, and carbohydrates, proteins may be host or virus derived
• Spikes: Carbohydrate-protein complexes that project from surface of envelope, means of attachment, identification and certain characteristics of virus
• Non-Enveloped: Capsid protects nucleic acid from nuclease enzymes in biological fluids and promotes virus’s attachment to susceptible host cells.

Question 6

Describe morphology of virions

Answer 6

• Helical: Long rods, rigid or flexible, viral nucleic acid found within a hollow, cylindrical capsid that has a helical structure (rabies and Ebola)
• Polyhedral: Many-sided viruses, capsomere’s of each face form an equilateral triangle (adenovirus / poliovirus)
• Enveloped: Envelope present, roughly spherical
• Naked viruses: No envelope
• Complex: Complicated, head is a polyhedral (nucleic acid), tail sheath is helical (contains tail fibres, plate, pin)

Question 7

Describe viral size

Answer 7

• Viral Sizes: Determined with aid of electron microscopy, range from 20-1000 nm, small relative to bacteria and eukaryotic cells

Question 8

What is the classification / taxonomy of viruses

Answer 8

• Since viruses can mutate so quickly, it can be difficult to classify them into a genus and a species epithet using binomial nomenclature system
• Families and Genre: Viral genetics, chemistry, morphology and mechanism of multiplication
• Family names = -viridae
• Genus names = -virus
• Order names = -ales
• Common names are used for species and subspecies are designated by a number
• Example: Herpesviridae, Herpesvirus and Human herpes virus HHV-1, HHV-2, HHV-3
• Example: Retroviridae, Lentivirus and Human immunodeficiency virus HIV-1, HIV-2
• Viral Species: A group of viruses sharing the same genetic information and ecological niche (host)

Question 9

Describe the discovery of new viruses

Answer 9

• Developments in genome sequencing allowed detection of new viruses, understand their diversity
• Abundance of viruses living in oceans, learning more about the mutualistic symbioses that occur between living organisms and viruses
• Influence of viruses on mammalian physiology and health

Question 10

How are bacteriophages grown

Answer 10

• Bacteriophages: Grown in suspensions of bacteria in liquid media or in bacterial cultures on solid media (agar / plaque method)
• Plaque Method: Bacteria in area of virus are infected, die by cell lysis (plaque), each plaque corresponds to a single virus, concentration of viral suspension = number of plaque forming units (PFU)

Question 11

How are animal viruses grown

Answer 11

• Living Animals: Mice, rabbits, and guinea pigs, experiments to study immune response to viral infections, animal inoculation
• Embryonated Eggs: Convenient and inexpensive form of host, injection of viral suspension, once most widely used method of isolating and growing viruses (used for some vaccines)
• Cell Cultures: Replaced embryonated eggs, cells grown in homogenous culture media in lab, continuous cell lines maintained indefinitely, tissue treated with enzymes to separate cells, suspension and virally infected cells are detected via deterioration (cytopathic effect CPE)

Question 12

How are viruses identified

Answer 12

• Cytopathic Effects: Viruses infecting a monolayer of cells causing them to deteriorate as they multiply
• Serological Tests: Detect antibodies against viruses in a patient, use antibodies to identify viruses in neutralisation tests, viral haemagglutination, and Western blot
• Nucleic Acids: RFLPs (restriction fragment length polymorphisms) and PCR (polymerase chain reaction)

Question 13

What is the lytic cycle (multiplication of bacteriophage)

Answer 13

• Multiplication: Must invade a host cell and take over host’s metabolic machinery, one step growth curve
• Lytic Cycle: Multiplication method, ends in cell lysis and death of host cell, T-even bacteriophages (T2, T4, and T6) have been studied extensively in their host, E. coli

Question 14

Describe the steps in the lytic cycle (multiplication of bacteriophage)

Answer 14

• Attachment: Phage attaches by tail fibres to host cell
• Penetration: Phage lysozyme opens cell wall; tail sheath contracts to force tail core and DNA into cell
• Biosynthesis: Production of phage DNA and proteins
• Maturation: Assembly of phage particles
• Release: Phage lysozyme breaks cell wall

Question 15

What is the lysogenic cycle (multiplication of bacteriophage)

Answer 15

• Lysogenic Cycle: Multiplication method, ends in cell lysis and host cell remains alive, bacteriophage l (lambda) is a well studied lysogenic phage
• Lysogeny: The phage remains latent (inactive) and participating bacterial host cells are lysogenic cells

Question 16

Describe the steps in the lysogenic cycle (multiplication of bacteriophage)

Answer 16

• Initial Stages: Phage attaches to host cell and injects DNA, phage DNA circularises
• Integration: Phage DNA integrates within bacterial chromosome by recombination becoming a prophage
• Reproduction: Lysogenic bacterium reproduces normally, many cell divisions, replicates prophage DNA (phage conversion)
• Excision: Occasionally the prophage may excise from the bacterial chromosome by another recombination event initiating the lytic cycle

Question 17

What are 3 outcomes of the lysogenic cycle

Answer 17

• Immunity: Lysogenic cells are immune to reinfection by the same phage
• Phage Conversion: The host cell may exhibit new properties.
• Specialised Transduction: Certain bacterial genes can be picked up in a phage coat and transferred to another bacterium, mediated by a lysogenic phage (packages bacterial DNA and own DNA in same capsid)

Question 18

How does multiplication of animal viruses occur

Answer 18

• Differs to Bacteriophages: Variation in attachment site, method of entry, uncoating and biosynthesis
• Variation to Central Dogma: Genetic information not always expressed using central dogma, some have a dsDNA genome (DNA, RNA, protein) while others have a ssDNA, dsRNA or ssRNA genome
• The nature of the genome determines how the genome is replicated and expressed as viral proteins

Question 19

Describe biosynthesis of DNA viruses

Answer 19

• Attachment: Viruses attach to cell membrane proteins / glycoproteins
• Entry: Capsid enters by receptor mediated endocytosis or fusion
• Uncoating: By viral or host enzymes, enzymatic removal of capsid proteins
• Biosynthesis: Production of nucleic acid and proteins in nucleus (DNA virus) or cytoplasm (RNA virus)
  DNA virus, dsRNA, -ssRNA (antisense), +ssRNA (sense), dsRNA or retrovirus, latent / lytic phase of viral life cycle, replicate differently
• Maturation and Release: Enveloped viruses bud out, non enveloped viruses rupture plasma membrane

Question 20

Describe biosynthesis of RNA virus (+ssRNA)

Answer 20

• Synthesise proteins directly from their + strand

- + strands serve as mRNA and are incorporated into capsid proteins

Question 21

Describe biosynthesis of RNA virus (-ssRNA)

Answer 21

• Host ribosomes cannot translate it until the -ssRNA is replicated into +ssRNA by viral RNA-dependent RNA polymerase (RdRP)
• The newly synthesised +ssRNA copies can then be translated by cellular ribosomes

Question 22

Describe biosynthesis of RNA virus (dsRNA)

Answer 22

• mRNA is produced inside capsid and released into cytoplasm of host, RNA polymerase initiates production of -ve strands from dsRNA incorporated in new viral genome

Question 23

Describe biosynthesis of RNA virus retrovirus (+ssRNA)

Answer 23

• An alternative mechanism for viral nucleic acid synthesis is observed in the retroviruses (+ssRNA)
• ssRNA (HIV) carry enzyme reverse transcriptase within the capsid, synthesises a complementary ssDNA (copyDNA), using +ssRNA genome as a template
• The ssDNA is then made into dsDNA, which can integrate into the host chromosome and become a permanent part of the host
• Integrated viral genome is called a provirus
• The virus now can remain in the host for a long time to establish a chronic infection
• The provirus stage is similar to prophage stage in a bacterial infection during the lysogenic cycle.
• However, unlike prophage, the provirus does not undergo excision after splicing into the genome

Question 24

What is cancer, types and its mechanisms

Answer 24

• Viral Cancer: May develop long after a viral infection, not contagious
• Sarcoma: Cancer of connective tissue
• Adenocarcinomas: Cancers of glandular epithelial tissue
• Process: Activated oncogenes transform normal cells into cancerous cells, transformed cells have increased growth, loss of contact inhibition, tumour-specific transplant antigens, and T antigens, genetic material of oncogenic viruses becomes integrated into host cell’s DNA

Question 25

What are examples of oncogenic DNA / RNA viruses

Answer 25

• DNA: Adenoviridae, herpesviridae, poxviridae, papovaviridae and hepadnaviridae
• RNA: Retroviridae, viral RNA is transcribed to DNA, which can integrate into host DNA, HTLV-1 and HTLV-2

Question 26

What are the types of viral infections

Answer 26

• Persistent Infection: Occurs when a virus is not completely cleared from system of host but stays in tissues or organs, may remain silent or undergo productive infection without seriously harming host (Herpes Simplex, EBV, Hepatitis C)
• Latent Infection: Not all animal viruses undergo replication by the lytic cycle, some viruses remain dormant inside cell in latency, can cause an acute infection before becoming dormant (Chicken pox, shingles or herpes virus)
• Chronic Infection: A disease with symptoms that are recurrent or persistent over a long time, some viral infections can be chronic if the body is unable to eliminate the virus (HIV-1)

Question 27

What is a prion / describe their history

Answer 27

• Prion: Proteinaceous Infectious particle, inherited and transmissible by ingestion, transplant, and surgical instruments, cause disease in humans and animals, involve degeneration of brain tissue
• Prion diseases = result of an altered protein, mutation in normal gene for PrPC or contact with an altered protein (PrPSc)
  disease (Creutzfeldt-Jakob)
• PrPC: Normal cellular prion protein, on cell surface, involved in regulating cell death
• PrPSc: Scrapie protein, accumulates in brain cells, forming plaques

Question 28

Describe plant cells, plant viruses and viroids

Answer 28

• Plant Cell: Impermeable cell wall, protection from disease
• Plant Virus: Enter through wounds or via sap sucking insects or other plant parasites (nematodes, fungi)
• Viroids: Short pieces of infectious naked RNA, no protein coat, RNA does not code for any proteins (potato spindle tuber viroid - PSTV)

Question 29

What are the differences between bacteria and viruses, viruses are / have;

Answer 29

• Intracellular parasite
• No plasma membrane, no binary fission
• Can pass through bacteriological filters
• Possess DNA or RNA, not both
• No ATP generating metabolism or ribosomes
• Not sensitive to antibiotics
• Sensitive to interferon