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