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Virology - Chapter 13

Not responsible for details of Protein & genome synthesis pp 399-401

A little history…

“Filterable viruses”

Bacteriophages

Wendell Stanley and TMV 1935

Advent of electron microscopy

How small

Small pox virus in cellCrystalized polio virus

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Fundamental Properties of Viruses

1) no metabolism

2) obligate intracellular pathogens

3) no membrane transport

4) replicate by “self-assembly”

5) genome of RNA or DNA

Classification of viruses-- Not included in Kingdom system-- Not classified above Order

Naming key trait of group member-- Herpesviridae (‘herpes’ like viruess)-- Filovirodae (‘filament’ like viruses

Sizes and surfaces of some viruses

Virology and AIDS 3

Virus Structure

The protein “capsid”

Common capsid shapes

rod (helical)

icosahedron

Capsomeres

Human rhinovirus

poliovirus

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Some more complex viruses

Enveloped viruses

HIV structure

Bacteriophages

Herpes virus

Receptors

Influenza virus

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Influenza(in chapter 22)

Key surface antigensHemaglutinin – HNeuraminidase – N

-- numbered 1,2,3, etc-- H3N2, H1N1, H1N5,

H & N antigens change types periodically

Minor genetic changes seasonal flu

Major genetic changes pandemic flu ??

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Seasonal ‘Flu’~36K deaths~200,000 hospitalizations

Why is there a ‘Flu season’?:social interactionsenvironmental conditions

Spread of new forms

H and N change slightly annually-- slightly different forms of viruses-- different “mixes” of forms

= “Antigenic drift”-- minor mutations in H and N genes

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Pandemic Influenza

“Antigenic-Shift” can occur-- DNA segments recombine-- in animal hosts

Challenges to controlVaccine development timeProduction capacity DistributionEconomics

Virology and AIDS 8

How do viruses enter cells?

Bacteriophages

animal viruses

membrane fusion vs endocytosis

uncoating

T4 infection

Influenza penetration

Modes of cell entry

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How do viruses replicateinside of cells?

1)The simple way – “Lytic cycle”

Measles virusBacteriophage

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Viral replication type 2

“Lysogenic cycle”

Viral DNA becomes part of host cell DNA

Latency

Some diseases caused by lysogenic viruses

Herpes RubellaChickenpox HPV infections

Measles MumpsHepatitisHIV

Ancient infections = ~ 8% of human genome

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Viruses and latency

Herpes (Herpes simplex virus)HSV-I : oral fever blistersHSV-II: genital herpes

Induction

Chickenpox (varicella-zoster virus)-- similarities to Herpes

HSV infection

Virology and AIDS 12

How can viruses cause cancer?

Human papilloma viruseswartscervical cancer

Hepatitis B and Cliver cancer

Epstein-Barr‘Mono’ (-nucleosis)lymphoma/leukemia

Oncogenes

Chronic inflammation

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HIV and AIDS

Virus anatomy

Target cells-- T-cells, etc

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HIV uses lysogenic cycle, but……it’s a “Retrovirus”

Reverse transcriptaseRNA DNAhigh mutational rates

CD4 & coreceptorsT-cells & macrophagesStages of infectionIntegrase and Protease

HIV replication & Drugs

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What are the clinical stages of an HIV infection?

Stages of disease

1. Acute Phase

2. Chronic Phase

3. AIDS-- T-cells < 200 /mm3

-- AIDS-associated disease(s)

HIV in bloodCD4 (helper) T cell countAntibody against HIV

Primary infection

Clinical latency

Opportunisticdiseases

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AIDS-associated diseases

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Control of viral infections(or lack thereof)

Antibiotics don’t work

Synthetic drugs-- symptoms-- low replication

Anti-HIV therapy

1) reverse transcriptase inhibitors-- AZT, ddl, ddc, etc-- nucleotide analogs

2) protease inhibitors

3) combinational drug therapy

What about an AIDS vaccine??

Virology and AIDS 18

AIDS Epidemiology

Prevalence (vs Incidence)

HIV CladesA, B, C, etc

Transmission

Cost of AIDS drugs

Health care issues

HIV prevalence (WHO 2010)

Virology and AIDS 19

Viroids and Prions ‘molecular pathogens’

Viriodspotato tuber spindle virus

(it isn’t)replication

Prions TSE: transmissable spongiform

encephalopathyScrapieKuruBSE: Mad cow disease