S.M Lecture 2

Question 1

Classification of Polioviruses

Answer 1

• Family - Picornaviridae (150 varites)
• Genus - 5 Genera, Rhinovuris, Hepatovirus, Cardiovirus, Apthovirus, Enteroviru (includes poliviruses)
• Species (Polio Virus)

Look at slide 7 for more on genus

Question 2

Characteristics of Polioviruses

Answer 2

• Small (30nm).
• 3 serotypes (Type I, II, or III)
• Single strand “+ sense” RNA
• Nonenveloped (Naked)
• Icosahedral Capsid symmetry
• Capsid is resistant to acidity, & detergents
• 4 components to capsid: VP1 (blue), VP2 (red), VP3 (yellow), VP4 (internal) proteins
• Xray crystallography reveals a canyon about 5-fold axis of symmetry
• Causes - paralytic poliomyelitis
• Transmission: Faecaloral

Question 3

Paralytic poliomyeltitis

Answer 3

• Depicted in Egyptian wall painting
• Most polio infections are unapparent/mild 1-2% reach CNS…high fever, back pain, muscle spasms (non paralytic poliomyelitis)
• In 0.1% of cases…partial/complete muscle paralysis when relaxed (paralytic poliomyelitis)
• If paralysis remains after months becomes permanent
• Destruction of large motor neurones causes acute flaccid paralysis (AFP)

Question 4

Cure for Polio - salk vaccine

Answer 4

• 1955 - injectable salk vaccine.
• Salk vaccine - formalin inacticated at neutral pH.
• Probelm as not all vaccine as attenuated

Attenuated microorganisms can be used in vaccines, where they stimulate an immune response without causing disease, and can provide long-lasting protection against future infections by the same microorganism.

Question 5

Cure for Polio - Sabin

Answer 5

• 1963 Sabin Vaccine
• Also known as the oral polio vaccine (OPV)
• The vaccine is made from 3 weakened, live polio virus strains, which are given orally in a sugar cube or liquid drops.
• The strains are attenuated meaning that they replicate but do not cause disease
• Developed by Albert Sabin

Question 6

Innactivated Polio Vaccine

Answer 6

• IPV contains polioviruses of three types which have been inactivated by formaldehyde. It is only available as a combination vaccine

Question 7

Tropism

Answer 7

The pattern of host cells which a virus can invade and replicate in (i.e. the biological niche)

Question 8

How is tropisim determined?

Answer 8

Tropism is determined by the host cells’ to viral entry (often expression of a receptor), and whether the cell is susceptibility permissive for replication (intracellular biochemistry)

Question 9

Poliovirus tropism

Answer 9

Gut M neurones, ( neurotropiccells ( enterotropic ), lymphoid cells.

Question 10

Do all primate cells express the PV receptor?

Answer 10

• All primate cells express the PV receptor (PVR; CD155) (susceptible), but only gut, CNS and certain other cells are permissive
• Polio virus binds to receptor (PVR) on susceptible cells

Question 11

Poliovirus: Genome organisation

Answer 11

• single copy of genome (+ve sense)
• single open reading frame (very simple)
• untranslated regions (UTR), capsid proteins, proteases, polymerase/RNA synthesis

Question 12

Poliovirus replication cycle

Answer 12

1. Virus binds to receptor (PVR) on susceptible cell & enters
2. Virus uncoats to release +RNA (Red)
3. +RNA translated to proteins (including polymerase) in permissive cell
4. Polymerase makes -RNA template from the +RNA
5. Now, +RNA made from -RNA template
6. Progeny virus assembled (using mRNA from 5 as its nucleic acid)
7. Cell Lyses and virus released

Question 13

Viremia

Answer 13

Virus in blood

Question 14

Classification of HIV virus

Answer 14

Family - retroviridae
Genus - Lentiviruses
Includes: Includes: HIV-1, HIV-2, SIV, FIV, BIV, Visna-Maedi virus
Species - HIV

Question 15

Which species of HIV infect humans?

Answer 15

HIV-1 and HIV-2

Question 16

HIV-1

Answer 16

• HIV-1 is thought to have originated in sourthern cameroon after jumping from wild chimps to humans during 20th century
• HIV-1 is more virulent. Easily transmitted and is the cause of the majority of HIV infections globally.

Question 17

HIV-2

Answer 17

• HIV2 may have originated from an Old World monkey of Guinea- Bissau, Gabon and Cameroon called the Sooty Mangabey
• HIV-2 is less transmittable and is largely confined to West Africa

Question 18

Hunter Theory

Answer 18

• A variety of theories exist explaining the transfer of HIV to humans, No single hypothesis is unanimously accepted
• The most widely accepted theory is so called ‘Hunter’ Theory….. transference of the virus from chimp to human when a human was bitten by a chimp or was cut while butchering one, and the human became infected
• Mutation of SIV

Question 19

Main sympthoms of AIDS

Answer 19

• Central: Encephalitis, Meningitis
• Eyes - Retinitis
• Lungs: - pneumocytis pneumonia, tuberclosis (multiple organs)
• Skin - Tumors
• Gastrointestinal: -Esophagitis, Chronic diarrhea,Tumors.

Question 20

Human Immunodeficiency Virus (HIV)

Answer 20

• Size = 110nm
• 2 copies of Single strand “ + sense” RNA
• Reverse transcriptase, integrase, protease
• Icosahedral Capsid symmetry
• Encased by a matrix protein within an envelope
• Envelope is lipid bilayer derived from host membrane but contains viral protein gp120
• Causes Acquired Immunodeficiency disease (AIDS)

Question 21

What way is HIV transmitted?

Answer 21

• Sexually transmitted (STD) or other exchange body fluids (i.v. drug abuse, vertical, unscreened blood donation)

Question 22

HIV: Genome organisation

Answer 22

• 2 copies of genome (9719 nucleotides)
• Genes encoded in all 3 reading frames
• alternative splicing
• Long terminal Repeats (LTR)
• 3 major genes: gag (capsid, matrix & protease), pol (RT & integrase), env (envelope proteins gp120)
• Accessory genes: nef, tat, vif (regulatory)

Question 23

HIV Tropsim

Answer 23

• primate cells expressing CD4 (such as helper CD4+ T cells) and macrophages (M-tropic)
• Also, either/or the chemokine receptor CCR5 (macs R5 HIV) or CXCR4 (T-cells X4 HIV)
• Lymphotropic
• HIV infection

Question 24

What does it mean that HIV is lymphotropic?

Answer 24

• HIV (Human Immunodeficiency Virus) is lymphotropic, which means it has a particular affinity for targeting the lymphatic system.
• HIV primarily targets and infects CD4+ T cells, which are a type of white blood cell that plays a critical role in the body’s immune system

Question 25

What are the four mechanisms for HIV?

Answer 25

1. direct viral killing of infected cells 2. increased rates of apoptosis in infected cells 3. killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells. 4. Death of uninfected CD4 'bystander cells' cells by cell suicide

Question 26

HIV Replication cycle

Answer 26

1. Virus binds to receptor (CD4, CCR5, CXCR4, on helper T cell) 2. Viral core (capsid) enters cell & releases +RNA 3. +RNA is converted to DNA by RT 4. +/- DNA is transported to nucleus and integrated into host genome (Provirus) 5. mRNA for viral proteins & viral genomes made from provirus +/- DNA template 6. Progeny virus assembled at cell surface 7. Immature virus buds from cell then matures

Question 27

Reasons for genetic variability...evasion of host immune system

Answer 27

1. Very fast replication cycle, with the generation of 10 every day, 2. High mutation rate of approximately 3 x 10-5 per nucleotide base per cycle of replication 3. Recombinogenic properties of reverse transcriptase Thus...many variants of HIV are present in a single infected patient in the course of one day.