08 lecture 17 - human viruses

8/8/2019 08 Lecture 17 - human viruses

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Viral replication DNA viruses Class I dsDNA viruses production of mRNA and

genome replication occurs as it would from the hostgenome eren v ruses use eren s ra eg es oensure viral mRNA is expressed in preference to hostcell mRNA

Class II ssDNA must synthesise complementaryDNA strand before mRNA can be produced so virusesform a dsDNA intermediate (using host cell enzymes)during replication intermediate used for transcription.ds-intermediate also used to re licate enome one

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strand becomes the genome and the other is discarded.

Class VII partially dsDNA but replicate through a RNAintermediate involves use of reverse transcriptase. EgHepatitis B virus hepadnavirus (see later)

Formation of mRNA and newgenomes DNA viruses

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Family Pox Herpes Adeno Papova Parvo Hepadna

Genome ssDNA Partial dsDNA

Capsidsymmetry

Complex

Examples of DNA Viruses

Envelope es

e.g. Vaccinia virus Herpessimplexvirus 2

Humanadenovirus

Papilloma HepatitisBAdeno-Associated

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MolluscumContagiosum

Family Corona Toga/Flavi Picorna Calici RetroGenome Diploid (+) RNA

Capsid symmetry Helical

Envelope Yes-

Positive Sense RNA Viruses

. .virus

Hepatitis C virus Hepatitis A virus

Hepatitis E virus

-

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Family Paramyxo Rhabdo Filo Orthomyxo Arena Bunya ReoGenome ss(-) RNA

segmentsss(+) or (+/-)segments

ss(+) or (+/-)segments

ds RNAsegments

Capsid Icosahedral

Negative Sense RNA Viruses

symmetryEnvelope No

e.g. MeaslesMumpsPara-influenza

Rabies virus Ebola virus Influenzavirus

Lassa virus Hanta virus Rotavirus

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Viral replication in eukaryotic cells No compartments in prokaryotes transcription of mRNA can lead

directly to translation

nucleus, translation in the cytoplasm So

DNA viruses using host polymerases must replicate in the nucleus Other DNA viruses (pox, herpes viruses) replicate in the cytoplasm

Transcripts from eukaryotic genes must be processed andtransported to the cytoplasm before they can be used as mRNA some intermediate processing steps are required to allow bindingof mRNA to the ribosome

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So Genomes of positive stranded RNA viruses must be in a processed

state in the virion if the RNA is to serve directly as mRNA


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Attachment Viruses attaches to cellmembrane

Multiplication of Animal viruses

Penetration By endocytosis or fusion Uncoating By viral or host enzymes Biosynthesis Production of nucleic acid and

proteins

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a ura on uc e c ac an caps

proteins assembly Release By budding (enveloped viruses)

or rupture

Fig. 14.8

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Fig. 14.11 Release of envelopedvirion

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Effect of animal viruses on cells

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Lytic infections

ExampleInfluenza Orthomyxoviridae ssRNA (-) Baltimore Class V Linear genome, RNA in 7 or 8 strands

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Helical nucleocapsid

Enveloped virus

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Structure of influenza virus. The diagram illustrates the main structural features of thevirion. The surface of the particle contains three kinds of spike proteins: thehemagglutinin (HA), neuraminidase (NA), and matrix (M2) protein embedded in a lipidbilayer derived from the host cell and covers the matrix (M1) protein that surrounds the

viral core.. (From Fields Virology, 4th ed, Knipe & Howley, eds, Lippincott Williams& Wilkins, 2001, Fig. 47-2)


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Replication of Influenza A virus1. A virion attaches to the host cell membrane

via HA and enters the cytoplasm byreceptor-mediated endocytosis

and the endosome membranes..

2.The major envelope protein M1 dissociatesfrom the nucleocapsid and viral RNAsegments are translocated into the nucleus

3. In the nucleus, the viral polymerasecomplexes transcribe (STEP 3a) andreplicate (STEP 3b) the viral RNA segments

4. Newly synthesized mRNAs migrate tocytoplasm where they are translated intoviral proteins

5a. Newly synthesised M1 viral proteins move tothe nucleus - bind freshly synthesized

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copies of viral RNA segments.5 b. Posttranslational processing of HA, NA, and

M2 includes transportation via Golgiapparatus to the cell membrane

6. The newly formed nucleocapsids migrate intothe cytoplasm - interact via M1 with a regionof the cell membrane where HA, NA and M2have been inserted

7. Then the newly synthesized virions bud frominfected cell. NA destroys the sialic acidmoiety of cellular receptors, therebyreleasing the progeny virions.

Influenza A hemagglutinin and neuraminidase subtypes

22Fields Virology, 4th ed, Knipe & Howley, eds, Lippincott Williams & W ilkins, 2001, Table 47-1


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Influenza A reservoir

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The reservoir of influenza A viruses. The working hypothesis is that wild aquatic birds are the primordial reservoir of all influenza virusesfor avian and mammalian species. Transmission of influenza has been demonstrated between pigs and humans (solid lines). There isextensive evidence for transmission between wild ducks and other species, and the five different host groups are based on phylogeneticanalysis of the nucleoproteins of a large number of different influenza viruses. (From Fields Virology, 4th ed, Knipe & Howley, eds,Lippincott Williams & Wilkins, 2001, Fig. 47-3.)

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Pandemics

1918(1)

Spanish flu(H1N1viruses likeswine flu)

Possible emergence from swine or anavian host of a mutated H1N1 virus

Pandemic with >20 million deathsglobally

1957(2)

Asian flu(H2N2)

Possible mixed infection of an animalwith human H1N1and avian H2N2 virusstrains in Asia

Pandemic, H1N1virus disappeared

1968(2)

Hong Kongflu (H3N2)

High probability of mixed infection of an animal with human H2N2 and avianH3Nx virus strainsin Asia

Pandemic, H2N2 virus disappeared

1977(3)

Russian flu(H1N1)

Source unknown but virus is almostidentical to human epidemic strainsfrom 1950. Reappearance detected atalmost the same time in China andSiberia

Benign pandemic, primarilyinvolving persons born after the1950s. H1N1 virus has cocirculatedwith H3N2 virus in humans since1977

Incidents with limited spread

1976(4)

Swine flu(H1N1)

United States/New Jersey. Virusenzootic in U.S. swine herds since atleast 1930

Localized outbreak in military trainingcamp, with one death

1986(5)

(H1N1) The Netherlands. Swine virusderived from avian source

One adult with severe pneumonia

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1988(6)

Swine flu(H1N1)

United States/Wisconsin. Swinevirus

Pregnant woman died after exposure tosick pig

1993

(7)

(H3N2) The Netherlands. Swine reassortant

between old human H3N2 (1973/75-like) and avian H1N1

Two children with mild disease. Fathers

suspected to have transmitted the virus tothe children after having been infected bypigs.

1995(8)

(H7N7) United Kingdom Duck virus One adult with conjunctivitis

1997(9)

Chickenflu (H5N1)

Hong Kong Poultry virus 18 confirmed human case, 6 deaths

Cumulative number of confirmed human cases of avianInfluenza A/(H5N1) reported to WHO

18 June 2008

C o u n t r y2 0 0 3 2 0 0 4 2 0 0 5 2 0 0 6 2 0 0 7 2 0 0 8 To t a l

c a se s d e a t h s c a se s d e a t h s c a se s d e a t h s c a se s d e a t h scase

sd e a t hs c a se s d e a t h s c a se s d e a t h s

Azerbaijan 0 0 0 0 0 0 8 5 0 0 0 0 8 5

Bangladesh 0 0 0 0 0 0 0 0 0 0 1 0 1 0

Cambodia 0 0 0 0 4 4 2 2 1 1 0 0 7 7

China 1 1 0 0 8 5 13 8 5 3 3 3 30 20

Djibouti 0 0 0 0 0 0 1 0 0 0 0 0 1 0

Egypt 0 0 0 0 0 0 18 10 25 9 7 3 50 22

Indonesia 0 0 0 0 20 13 55 45 42 37 18 15 135 110

Iraq 0 0 0 0 0 0 3 2 0 0 0 0 3 2

Lao People'sDemocratic 0 0 0 0 0 0 0 0 2 2 0 0 2 2

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i

RepublicMyanmar 0 0 0 0 0 0 0 0 1 0 0 0 1 0

Nigeria 0 0 0 0 0 0 0 0 1 1 0 0 1 1

Pakistan 0 0 0 0 0 0 0 0 3 1 0 0 3 1

Thailand 0 0 17 12 5 2 3 3 0 0 0 0 25 17

Turkey 0 0 0 0 0 0 12 4 0 0 0 0 12 4

Viet Nam 3 3 29 20 61 19 0 0 8 5 5 5 106 52

To ta l 4 4 4 6 3 2 9 8 4 3 1 1 5 7 9 8 8 5 9 3 4 2 6 3 8 5 2 4 3

http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_06_19/en/index.html


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Flu could hitch a ride on banknotes16:02 22 June 2007NewScientist.com news service

Transmission of influenzaDirect contactAerosol

,The flu virus persists so well on banknotes that money could helpspread the next pandemic, researchers say.

Yves Thomas and colleagues at the University Hospitals of Genevain Switzerland dripped various strains of flu virus including somethat were circulating during winter 2007 onto Swiss banknotesand left them at room temperature for varying amounts of timebefore testing for live virus.

Some strains of flu lasted onl two hours, but the most common flu,

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H3N2, lasted up to 72 hours. However, all the strains lasted longerwhen they were dripped onto the notes along with human nasal mucus.

Some lasted as long as 17 days. One strain that lasted only twohours on its own lasted 24 hours in mucus.

Lytic infectionPoliovirus Picornaviridae ssRNA virus (+) Baltimore

Class IV Simple icosahedral

nucleocapsid Very small virus Polio Almost eradicated from the

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wor y e ec ve vacc na onprogram http://www.polioeradication.orTransmission Common vehicle (water)


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Latent infectionsHerpes simplex virus and varicella-zoster virus Herpesviridae s v rus a t more ass Icosahedral nucleocapsid Enveloped cold sores (herpes simplex virus) and chicken pox and shingles

(varicella-zoster virus) Virus remains latent in the neurones of the sensory ganglia from

which they emerge to cause infections of the skin

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Transmission Direct contact (chicken pox scabs) aerosol


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Oncogenic viruses Cancer the result of the loss of the cells normal control

of its growth Growth & division of cells regulated by at least 2 types of

genes Proto-oncogenes promote growth Tumour repressor genes restrain growth

Changes in either can lead to uncontrolled growth andso cancer

Initiation event of cancer process can be the activation of

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a pro o-oncogene n o an oncogene or nac va on o etumour repressor gene Not always possible to prove direct link with oncogenic

virus


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normal transformed by virus

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contact-inhibited pile up, rounded

Viruses associated with cancersCancer virus family Genome in

virion

Adult T-cellleukaemia

Human T-cellleukaemia virustype 1

Retroviridae ss RNA (+)Baltimore VI

Burkittslymphoma

Epstein-Barr virus Herpesviridae ds DNABaltimore 1

Nasopharyngeal Epstein-Barr virus Herpesviridae DNA

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Hepatocellularcarcinoma

Hepatitis B virus Hepadnaviridae ds DNABaltimoreVII

Skin & cervicalcancers

Papilloma virus Papillomaviridae ds DNABaltimore I


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Hepadnavirus Hepatitis B Very small genome 3.4 kb enome part a y s- stran ncomp ete, ot ave gaps Once inside host cell viral DNA polymerase (carried in the virion)

completes the replication Polymerase is a versatile protein contains DNA polymerase as

well as reverse transcriptase and acts as a protein primer forsynthesis of one of the DNA strands

Replication of the genome involves transcription by host RNApolymerase viral reverse transcriptase then copies this into a DNAmolecule

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Transmission Direct contact body fluids of infected person

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Chronic HBV infection can lead to cirrhosis and then to liver cancer


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Retroviruses

Retroviridae ssRNA (positive strand) Baltimore Class

VI Enveloped viruses Replicate via DNA intermediate reverse

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ranscr p ase

First viruses to be associated with cancer HIV

Retrovirus Cartoon of a

Genetic map of atypical retroviralgenome

Genetic map of Roussarcoma virus

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retrov rus t at causesmalignant tumours inbirds


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2

Replication of a retrovirus

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Transmission of HIV Sexual transmission.

Transfusion of infected

blood and blood

products.

Vertical transmission.

Needle sharin amon

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injecting drug users.

Occupational exposure.


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2

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Transmission of viral diseases1. Airborne transmission examples viruses shed from the

upper respiratory tract (common cold, influenza); viruses shedrom s n es ons eg c c en pox, erpes v ruses .

2. Faecal-oral transmission viruses shed in the faeces transmitted by contaminated water or food eg Hepatitis A,rotavirus, enteroviruses (eg polio), norovirus.

3. Body fluids transmission viruses transmitted in blood orother body fluids eg Hepatitis B and C; HIV;

4. Vector transmission viruses carried by insects andarthropods arboviruses ( ar thropod bo rne viruses). Most

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arboviruses are normally carried by birds and animals(subclinical infections) and spread to people by insects orarthropods.


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Transmission of viral infections5. Foetal and neonatal transmission virus infections in the

mother that can cause serious problems for the foetus orneona e.

Teratogenic effects Rubella (German measles) in the first trimester of pregnancy

congenital defects such as heart defects, blindness, mentalretardation;

Cytomegalovirus (CMV) depending on the stage of gestationand the status of the mother can result in death or prematurebirth or a range of congenital defects;

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. Vertical transmission Hepatitis B, HIV can be transmitted

from the mother to the neonate. Viral disease acquired at birth genital herpes in the mother

can lead to herpes encephalitis in the neonate.

08 lecture 17 - human viruses

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