Module 26 - Virology

Question 1

Differ between virus and virion.

Answer 1

While not inside an infected cell or in the process of infecting a cell, viruses exist in the form of independent particles. These viral particles, also known as virions, consist of:

(i) the genetic material made from either DNA or RNA, long molecules that carry genetic information;
(ii) a protein coat, called the capsid, which surrounds and protects the genetic material; and in some cases
(iii) an envelope of lipids that surrounds the protein coat.

Question 2

riDescribe the characteristics of the virion.

Answer 2

It contains a genome which may be DNA or RNA, single or double stranded, linear, circular or segmented.

Note: For RNA viruses, the genome can have + or - sense (+ sense is the same as mRNA)

Genome is packaged in a protective protein coat (capsid). Furthermore, it also has an envelope made of the host cell membrane modified to contain the virus proteins (which has glycoproteins responsible for cell interaction)

Question 3

What is the function of a capsid? Explain the concept of capsid symmetry.

Answer 3

Capsid has the function to protect the genome form breakdown by nucleases. Capsid proteins are assembled symmetrically around the nucleic acid to form either:

• an icosahedral capsid (composed of capsomers)
• helical capsid (enclosed in modified cell membrane envelope)

Question 4

Mention examples of viruses with icosahedral symmetry.

Answer 4

Adenovirus. Herpesvirus. Pappilomavirus

Question 5

Mention examples of virus with helical symmetry.

Answer 5

Mumps virus, influenza virus

Question 6

How are virus classified?

Answer 6

Viruses are classified into Families by

• Type of nucleic acid genome
• Strategy of replication (how is mRNA produced from genome?)
• Morphology of the virion

Families names end with …viridae

Genera, species, and types are distinguished by different arrangements of genes, or sizes of proteins, or serological reactions, and often on types of disease produced.

Question 7

Explain the method of the plaque essay.

Answer 7

In a plaque essay, a virus is added to a monolayer cell culture. The plaque arises due to cell death because of the virus (after which it is washed and stained).

Agar layer ensures virus only spread to neighbouring cells and not spread indiscriminately

Question 8

Describe the overview of replication cycle curve of virus.

Answer 8

Eclipse Period: a period where there is a decline of intracellular virus particle due to uncoating of virus during replication (no longer considered virus)

Latent period: period before lysis of cell or budding (releasing virus)

Question 9

Mention the stages in viral replication.

Answer 9

Question 10

Mention the two methods of which virus can enter a cell.

Answer 10

• Fusion with the plasma
• Endocytosis then endosome escape
  
  • Fusion with endosome
  • Genome passes through endosome bilayer
  • Lysis of endosome

All require interaction with a receptor on the host cell.

All results in uncoating and release of genome to replicate.

Question 11

Describe the Baltimore Classification

Answer 11

• • RNA requires transport of RNA-dependent RNA polymerase (structural part of virion)
• • RNA (=mRNA) transcripts and translates RdRP which synthesizes minus strans -> new + RNA strand
    
    • Some +RNA uses rvt to revert to dsDNA
• ssDNA and dsDNA both can use available DdRP in the host cell to produce mRNA

Question 12

How are envelopes on virus acquired?

Answer 12

Envelopes are acquired by budding through host cell membranes.

Note: Non-enveloped cells exits through lysis.

Question 13

Mention the types of the transmission method of viral pathogen.

Answer 13

• Respiratory or salivary spread
• Facial-oral spread
• Venereal spread
• Vector
• Vertebrate resevoir
• Vector-vertebrate reservoir

Question 14

Mention and describe an example of systemic respiratory tract viral infection.

Answer 14

Mumps virus (causes measles) replicates primarily in the epithelial cells of URT, bind to sialic acid receptors in the cell. Systemic infection ensues, involving virtually all organs including CNS (mild meningitis common). Characteristic salivary gland involvement (swelling).

Question 15

Explain how viruses can enter and replicate in the alimentary tract.

Answer 15

Virus can enter through either through ingestion (oral) or rectally. Ingested viruses can either:

• replicate in mouth and pharynx but not further down (herpes simplex)
• infect oropharynx and swallowed (rotavirus)
• progress into the circulation (enterovirus)

Viruses that are swallowed are usually acid and bile resistant and do not have an envelope.

Question 16

Mention and describe examples of viral infections of the alimentary tract through mouth/oropharynx.

Answer 16

• Herpes simplex virus 1: causes cold sores, acquired by direct contact of infected saliva with damaged skin of the mouth.
• Epstein-Barr virus: causes infectious mononucleosis (glandular fever), acquired by direct contact of infected saliva with oropharynx

Question 17

The _______________ viruses causes alimentary tract viral infection through fecal-oral spread.

Answer 17

Picornaviridae:

• Enterovirus
• Hepatovirus
• Rhinovirus

Question 18

Describe the pathogenesis of acute poliomyelitis.

Answer 18

1. Ingested in food or water
2. Infects tonsular and intestinal Peyer’s Patches cells (intestine)
3. Replicates and kills cells (since it doesn’t have envelope)
4. Invades subepithelial cells
5. Causes viremia and spreads throughout the body
6. Infects susceptible tissues bearing receptor (CD155), leads to infection of CNS (rare) -> motor neurons in the brain and spinal cord destroyed

Question 19

Differentiate disseminated infection and systemic infection.

Answer 19

Disseminated infection: spread beyond primary site

Systemic infection: many organs infected

Question 20

Mention the spread mechanisms of virus in the body.

Answer 20

• Local spread on epithelial cells
• subepithelial invasion and lymphatic spread
• spread via bloodstream (viremia)

Question 21

What factors determine that viral infections would lead to local or systemic infections?

Answer 21

• Availability of receptors for the virus
• Availability of cleavage-activating proteases
• Optimal temperature for replication
• Ability to withstand harsh conditions
• Polarized release (apical versus basolateral)
• Ability to replicate in macrophages and lymphocytes

Question 22

Mention the types of virus-induced changes in cells.

Answer 22

Question 23

Why do we feel sick because of a viral infection?

Answer 23

• Viral damage to tissues and organs
  
  • Killing of tissues by lytic virus
  • Loss of function
  • Cancer formation
• Consequences of immune response.
  
  • immunopathology
  • Immunosuppression

Question 24

Why can we get some diseases over and over again?

Answer 24

• ineffective immunity (warts)
• effective immunity but multiple serotypes of virus (rhinovirus)
• constantly envolving virus (influenza, HIV)

Question 25

How do viral genomes continually change?

Answer 25

* **Point mutation** or, if two closely related viruses infect the same cell * **Recombination:** exchange of nucleic acid sequence * **Reassortment:** swapping of segments for viruses that have segmented genome

Question 26

Mention an example of a viral disease that reappears, often in a different form.

Answer 26

It happens in cases of **latent infections**, such as the case in the Varicella-zoster virus. In some cases, after the initial infection (chickenpox), the virus is then cleared from the system. However, in the others, from the skin lesions, some of that virus travels up the nerve under the skin to the nerve bundle (dorsal root ganglion) in the form of its genome. When you get older and immune response wanes, it will emerge throughout all the nerve originating from that ganglion (herpes zoster/shingles).

Question 27

What is the aim of vaccination?

Answer 27

Most vaccination aims to establish a poll of memory T and N cells for more rapid and greater immune responses when the pathogen is encountered again (long-lived antibody responses). 1. Memory CD8+ T cells -\> killing of virus-infected cells by CTL 2. Memory B cells -\> neutralisation of virus by antibody * Neutralising AB directed against surface proteins * prevent attachment/subsequent stages of infection * promote opsonisation or 'Ab+complement' lysis 3. Memory CD4+ T cells -\> help B cells make antibody, help cytotoxic T cell develop into memory cells

Question 28

Define antigenic drift.

Answer 28

Antigenic drift refers to the accumulation of mutations in the sites **to which the antibodies bind.** It may occur due to a spontaneous/random point mutation in the viral RNA genome as a result of the error-prone RdRP (alongside the process of selection)

Question 29

Compare and contrast of polio vaccines (Sabin v Salk)

Answer 29

Sabin (Oral Polio Vaccine): * advantage: easy to administer. stimulate intestinal immunity, can spread to contact, inexpensive * disadvantage: can revert to virulence, possibly unsafe for immunodeficient, requires "cold chain" to keep it alive Salk (Inactivated Polio Vaccine): * advantage: does not cause disease, safe for immunodeficient, cold chain not required * disadvantages: must be injected, no intestinal immunity, more expensive

Question 30

Explain the mechanism of antiviral drugs.

Answer 30

Antiviral drugs work by inhibiting particular stages of viral replication.

Question 31

How do nucleosides analogs work? What determines its specificity for virus-infected cells?

Answer 31

It is an acyclovir compound used for herpesvirus infections. Acyclovir is a guanosine analogue (with an acyclic sugar). The phosphate group can be added to the hydroxyl group attached to the 5' Carbon to be incorporated into DNA. But the 3' hydroxyl group required to extend the DNA polymer is absent (terminating the DNA replication chain). This is specific to virus-infected cells, as **herpesvirus thymidine kinase enzyme** is required to add phosphate to Acyclovir. Without this, it can't be incorporated into DNA, hence not affecting normal cells.

Question 32

Mention the routes of entry of viruses.

Answer 32

Question 33

Rotaviruses infect the _____________ and causes \_\_\_\_\_\_\_\_\_. Mention a characteristic of the virus that allows this.

Answer 33

lining of intestine, diarrhoea The virus has multiple-shelled capsids, which allows the virus to survive passage through the gut.

Question 34

Where do viral genome usually replicate depending to the type of its genome?

Answer 34

RNA viruses replicates in the cytoplasm, while DNA viruses in the nucleus (except for influenza, HIV, poxvirus)

Question 35

Why are viral envelope often glycosylated?

Answer 35

Because they are trafficked through the ER and golgi (before deposited in the cell surface), where they are oftenly modified (such as glycosylated).

Question 36

Describe secondary viremia.

Answer 36

Viruses that are free in the bloos are vulnerable to circulating macrophages. Such viruses have evovlved to have **an amplification stage** in the liver, spleen, or endothelium to increase likelihood of survival. Primary viremia refers to the initial spread of virus in the blood from the first site of infection. After the amplification stage, **secondary viremia** occurs which resulted in infection of multiple sites.