Viruses and Avian and Swine Flu (Learning Objectives)
1 Define a virus as a biological entity and learn its properties1. Define a virus as a biological entity and learn its properties.2. Learn the biochemical nature of viral components: genome
(DNA or RNA), capsid, nucleocapsid, and envelope in some.3 L th b i f i l h t ith l3. Learn the basis of viral host range, with examples.4. Identify the role of viral surface proteins H & N in the life cycle
of influenza viruses and in their sub‐typing 5. Explain the roles of RNA polymerase error rate, genome
segmentation, and Type A broad host‐range in transmission of human to human seasonal flu and swine and avian to humans.
6 Id if h l f d i i i h6. Identify the role of random genetic mutations in human influenza epidemics and pandemics, and in transmission of avian flu to humans.
7 R i th l f G t i i i i t i i f bi d7. Recognize the role of Genotypic mixing in transmission of bird and swine influenza viruses to humans.
Viruses are genes packaged in proteinViruses are genes packaged in protein
– Biological non‐living entities
– Have no cytoplasm
– Cannot self‐replicate
– Cannot metabolize
Genetic material either– Genetic material either
DNA or RNA never both
VirusesViruses
• To replicate they need to infect a living cellTo replicate they need to infect a living cell
• Every living cells has one or more viruses that can infect it specificallycan infect it, specifically.
Basis of Host‐Range of Viruses
• Host range is determined by “lock-and-key” fit between virus surface and cellular receptors on host cellvirus surface and cellular receptors on host cell
• Most viruses infect only specific types of cells in one hostMost viruses infect only specific types of cells in one host Narrow host range with tissue specificity – cold viruses: upper respiratory tract cells.– HIV, AIDS virus: a certain white blood cell.
• Some have a broad host-range infecting multiple species – rabies
Genes of viruses are made of either DNA or RNAFl i RNA– Flu viruses are RNA
– Genital warts virus (HPV) and Herpes virus are DNA viruses
http://www cdc gov/STD/HPV/STDFact‐HPVhtm
Membranous
http://www.cdc.gov/STD/HPV/STDFact‐HPV.htm
envelope
RNA
Proteincoat
Glycoprotein spike
HPVInfluenza
Plant viruses are serious agricultural pestsM t l t i h RNA– Most plant viruses have RNA genomesEnter their hosts via wounds in the plant’s outer layers
Protein RNAProtein RNA
Figure 10.19
Emerging viruses threaten human healthEmerging viruses threaten human health
TEM 50,00
0
TEM 370
,000
Colorized T
Colorized T
Figure 10.20A, B
Ebola Virus (RNA) SARS Virus (RNA)
The AIDS virus– HIV is an RNA retrovirus
– It makes DNA using RNA template
– Inside a cell, HIV uses its RNA as a template to make a DNA f it lf hi h i t t i t th h tcopy of itself, which integrates into the host genome.
http://www.whfreeman.com/kuby/content/anm/kb03an01.htm
Envelope
Glycoprotein
Protein coat
RNA (two identical strands)
Reverse transcriptase
Influenza Virus structureInfluenza Virus structure
• Influenza virus is a segmented envelopedsegmented enveloped RNA virus with 7-8 separate nucleocapsids within an enveloped virus
• http://www.xvivo.net/zirus‐antivirotics‐condensed
(Spikes)(Spikes)
Influenza Type A subtypes
H: Hemagglutinin (Entry)(15 subtypes)
N N i id (E it) N ikN: Neuraminidase (Exit)(9 subtypes) H spike
N spike
Type A subtypes: H#N#
I fl Vi TInfluenza Virus Types
Infected Species
Disease spread
Reservoir Subtypes
Type A Multiple: humans, birds, pigs, horses,
l h l
EpidemicsPandemics
Wild Birds Many based on 2 viralseals, whales
& others
2 viral spikes
Type B humans Epidemics People Noneyp p
Type C humans(Mild disease)
Epidemics People None
Human Influenza Seasonal Epidemics
• Low fidelity of RNA Polymerase
• Mutations change surface structures (antigens)– Antigenic Drift
• Disease is caused byDisease is caused by– toxicity of viral products to cells
response of the immune system– response of the immune system
• Acquired Immunity q y
I fl Vi TInfluenza Virus Types
Infected Species
Disease spread
Reservoir Subtypes
Type A Multiple: humans, birds, pigs, horses,
l h l
EpidemicsPandemics
Wild Birds Many based on 2 viralseals, whales
& others
2 viral spikes
Type B humans Epidemics People Noneyp p
Type C humans(Mild disease)
Epidemics People None
Molecular Basis of avian and swine Flu virusMolecular Basis of avian and swine Flu virus transmission to humans
– Segmented genome
– Broad host‐range Type A flu viruses
Direct Transmission of Avian Flu to Humans
M i bl i j h i• Mutations enable it to jump to other species including humans
• Outbreak of human avian influenza due to close i h H5N1 T A i f d bi dcontact with H5N1 Type A infected birds.
Expansion of Host Range of dSegmented Viruses
Host‐range of influenza type A can also be modified by genetic mixing of nucleocapsids during assembly in a host cell
Genetic re‐assortment of viral nucleocapsids between human and non‐human influenzabetween human and non human influenza viruses
http://www.nfid.org/_old1/content/influenza/influenza_archive/acknowledgements/influenza.pdf
Genotypic Mixing of segmented virusesSwine
Assembly Release
Transmission of re‐assorted viruses
Bird flu or pig flu ird flu or pig flu• new to the human population • no neutralizing antibodies l di t id i d d i d• leading to epidemic and pandemic spread
Swine H5N1 & Avian H1N1 Flu virusesSwine H5N1 & Avian H1N1 Flu viruses
H1N1 –
• Mortality of 0.5 %
• Human human spread• Human‐ human spread
H5N1 ‐ ~50% mortality rate
• Does not easily spread from human to y phuman, yet
Drugs TamifluDrugs Tamifluhttp://www.pharmasquare.org/flash/Tamiflu.html#Virus
