S.M Lecture 2 Flashcards
Classification of Polioviruses
- 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
Characteristics of Polioviruses
- 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
Paralytic poliomyeltitis
- 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)
Cure for Polio - salk vaccine
- 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.
Cure for Polio - Sabin
- 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
Innactivated Polio Vaccine
- IPV contains polioviruses of three types which have been inactivated by formaldehyde. It is only available as a combination vaccine
Tropism
The pattern of host cells which a virus can invade and replicate in (i.e. the biological niche)
How is tropisim determined?
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)
Poliovirus tropism
Gut M neurones, ( neurotropiccells ( enterotropic ), lymphoid cells.
Do all primate cells express the PV receptor?
- 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
Poliovirus: Genome organisation
- single copy of genome (+ve sense)
- single open reading frame (very simple)
- untranslated regions (UTR), capsid proteins, proteases, polymerase/RNA synthesis
Poliovirus replication cycle
- Virus binds to receptor (PVR) on susceptible cell & enters
- Virus uncoats to release +RNA (Red)
- +RNA translated to proteins (including polymerase) in permissive cell
- Polymerase makes -RNA template from the +RNA
- Now, +RNA made from -RNA template
- Progeny virus assembled (using mRNA from 5 as its nucleic acid)
- Cell Lyses and virus released
Viremia
Virus in blood
Classification of HIV virus
Family - retroviridae
Genus - Lentiviruses
Includes: Includes: HIV-1, HIV-2, SIV, FIV, BIV, Visna-Maedi virus
Species - HIV
Which species of HIV infect humans?
HIV-1 and HIV-2
HIV-1
- 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.
HIV-2
- 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
Hunter Theory
- 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
Main sympthoms of AIDS
- Central: Encephalitis, Meningitis
- Eyes - Retinitis
- Lungs: - pneumocytis pneumonia, tuberclosis (multiple organs)
- Skin - Tumors
- Gastrointestinal: -Esophagitis, Chronic diarrhea,Tumors.
Human Immunodeficiency Virus (HIV)
- 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)
What way is HIV transmitted?
- Sexually transmitted (STD) or other exchange body fluids (i.v. drug abuse, vertical, unscreened blood donation)
HIV: Genome organisation
- 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)
HIV Tropsim
- 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
What does it mean that HIV is lymphotropic?
- 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
What are the four mechanisms for HIV?
- direct viral killing of infected cells
- increased rates of apoptosis in infected cells
- killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells.
- Death of uninfected CD4 ‘bystander cells’ cells by cell suicide
HIV Replication cycle
- Virus binds to receptor (CD4, CCR5, CXCR4, on helper T cell)
- Viral core (capsid) enters cell & releases +RNA
- +RNA is converted to DNA by RT
- +/- DNA is transported to nucleus and integrated into host genome (Provirus)
- mRNA for viral proteins & viral genomes made from provirus +/- DNA template
- Progeny virus assembled at cell surface
- Immature virus buds from cell then matures
Reasons for genetic variability…evasion of host immune system
- Very fast replication cycle, with the generation of 10 every day,
- High mutation rate of approximately 3 x 10-5 per nucleotide base per cycle of replication
- Recombinogenic properties of reverse transcriptase
Thus…many variants of HIV are present in a single infected patient in the course of one day.
