web viewstructure of virus itself ... ( avian leukemia virus ) and . complex virus : deltaretrovirus...

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12/5/2014 ARBOVIRUSES LECT # 30

FIRST OF ALL ,HOW TO CLASSIFY THE VIRUSES ??? -VIRUSES are classified depending on many aspects like:

1. DNA or RNA viruses 2. Enveloped or not 3. Site of infection 4. Host (animal, plant ,zoonosis) 5. Structure of virus itself

*we are going to talk mainly about these viruses that are mainly cause diseases in human and animals *one of the main important characteristics of these viruses that in their host ,in their original host ,generally they cause disease ,tumor. while if they are transmitted to a non-original host .they can cause a very severe disease and sometimes a killing disease .

So viruses in their host ….cause disease and some certain tumors . In the other non-original host…cause severe or killing disease- We will talk about these arboviruses which they are large groups :1. Etiology 2. Epidemiology and history 3. Pathogenesis and pathology 4. Clinical manifestation 5. Diagnosis 6. Treatment 7. Prevention and controls This group of viruses is a very very large group ,the name is taken from different words ARBO-VIRUSES :

AR: arthropod, which they are vectors ,which transmits the disease from human to animal and vis versa B: born viruses

Arthropod born viruses : which means viruses are transmitted by these arthropod Generally they are more than 600 different viruses and transmitted by arthropod vectors

*the definition of WHO of these viruses: -viruses maintained in nature principally or to important extent through biological transmission between susceptible vertebrate hosts by :

Hematophagus arthropod


Trans-ovarial transmission Venereal –transmission

In arthropods . Sometimes ,these viruses will be transmitted from arthropods + from the

ovas to the human or others . These viruses we can see them mainly in 3-families :

1) Toga-viruses 2) Bunya –viruses 3) Flavi-viruses

*each one has many types of viruses .for example togaviruses…they mainly cause encephalitis in animals ,,,examples: EEE: east equine encephalitis WEE: west equine encephalitis VEE: venezuelen equine encephalitis **equine : means horse ,which means ,they can cause encephalitis mainly in horse

Bunya-viruses , they can cause hemorrhagic fever ,rift-valley fever ,sand-fly fever Crimean –congo hemorrhagic fever(Cuz the arthropod can transmit these types of diseases ).

Flavi-viruses: causes :- fever :yellow/dengue -encephalitis(Japanese)

The main characteristics of togaviridae :-sindbis …they are transmitted +they are found mainly in the forest which there are a high rain +humidity -VEE -EEE-WEE Flavi-viruses:

*mainly they are :1) Dangue fever 2) Yellow fever 3) Japanese encephalitis


4) West-nile encephalitis 5) Sant. louis encephalitis 6) Russian spring-summer encephalitis 7) Powassan encephalitis

*these viruses are enveloped ,they are icosa-hedral If we look to the toga-viridae + flavi-viridae…..they are heat +detergent

labile (cuz they are enveloped ,the envelop is sensitive to heat + to the detergent (ether,alcohol)

They are icsahedral : size:40-75 nm for toga /40-45nm for flavi Genome:is +ve ,ssRNA ,directly give m-RNA

Bunya-viridae : again :they are heat +detergent labile because of the envelope

Helical in shape (-ve)ssRNA +segmented …this means it should develop a (+ve) strand

inorder to be able to give m-RNA

Reo-viridae : *no envelope ,so resistance to the heat and detergent *ds-RNA +segmented *icosahedral capsid shape

So the virus structure has 3-types of proteins It has three proteinsEnvelope proteinCore proteinMembrane protein : which they sever as antigenic characteristic for the virus which can invade the immune response or we can prepare the vaccine against these virus.

General Antigenic Properties of Flaviviral Proteins - 1

E-glycoproteinMost important flaviviral antigenVery immunogenic


Most serological assays detect reactivity with this proteinSo we use glycoprotein to diagnosis this group

Capsid Elicits primarily group-reactive antibody,it is not specific to ward this strain M-proteinVery small (75 a.a.)Embedded in the virion envelope membrane and not highly immunogenic

How these viruses replicate

The replication mainly if there is a receptor on the cell membrane (envelope ), the structure of envelope protein is lipoproteins belong to the host cell so generally it is part of host cell.1st step there will be a reaction of that virus to their receptor on the host cell and the lipid layer will be assochaited/dissochation with the cell membrane of the host cell then it will enter to the cell2nd step : after that , the virus will be uncapside by proteolytic enzyme ,the RNA will be released from there ,if it is( +ve) then it start to produce the proteins in Golgi apparatus ,ER of the host cell 3rd step :then all the component of virus after formation will be associated in to the capside 4th step :Then they bud- out the cell ((the cell will note be destroyed, instead of that there will be budding)) so these viruses will bud out the host cell ,they will take from cell membrane (lipo-protein )

Transmission

Japanese encephalitis, dengue, yellow fever, St. Louis encephalitis, EEE, WEE, VEE etc

Mosquitoes

Crimean-Congo haemorrhagic fever, various tick-borne

encephalitides etc.

Ticks

Sicilian sandfly fever, Rift valley fever.

Sandflies


Animal Reservoirs

Japanese encephalitis, St Louis encephalitis, EEE, WEE

Birds

Japanese encephalitisPigsYellow FeverMonkeysVEE, Russian Spring-Summer encephalitisRodents

Transmission of the Reservoirs

The most common route of infection is the bite of infectious mosquito it will take blood from the animals or from human and it well be transmitted to other reservoirs.

Other transmission modes where revealed in 2002 such as:

1)Blood Transfusion 2),Organ Transplantation3), Intrauterine 4) ,Percutaneous exposure (occ. exposure), 5)Breast milk (probable)

Transmission Cycles

e.g. dengue, urban yellow fever .

Reservoir may be in either man or arthropod vector.

In the latter trans-ovarial transmission may take place(from vector to its ova then to human)

*Man - arthropod –man(no animal INTERFERE)


e.g. Japanese encephalitis, EEE, WEE, jungle yellow

fever .The reservoir is in an

animal . The virus is

maintained in nature in a transmission cycle involving the arthropod vector and animal. Man becomes infected incidentally.

Both cycles may be seen with some arboviruses

such as yellow fever .

*Animal - arthropod vector - man (Human not the main person who get the infection)

Epidemiologic Feature

The major outbreaks coincided with the heavy rainfall or floods .

Seasonal: more common in summer, July to October

Infection provides lifelong immunity cause of lipoprotein and capside very strong immunogenic protein or if u give vaccine the person will be immune. .

Worldwide distribution More than 530 species, 150 pathogen to man

Pathogenesis

The nature of flavi-virus disease is determined primarily by:

The specific tropisms of the individual virus type( could cause fever ,hemorrhagic ,encephalitis)dpend on which virus we talking about to see the pathogen

The concentration of infecting virus: how much virus enter the body (few amount or large amount )

Individual host response to the infection : good ,compromised have other disease)


Generally , when the arthropode suck blood ,it gives the virus to human

Generally withen 2-3 days no signs & symptom will be just itching at the bit site

After 3-7 day the virus will go to the blood so cause viremia

When it cause viremia it can go to the liver and to the lymphocytes (it cause mild systemic disease ,fever ,common flue ,chills )

After one week or more we can see that there is production of Ab in the blood.

If there is enough Ab no more symptomif there is no enough Ab or immune compromised so the virus can go to brain and cause encephalitis ,yellow fever ,hepatitis ,hemorrhagic fever

summery: virus from bite site …go to macrophage –blood circulation…2 possibility

1)enough Ab …no secondary invasion ..mild symptom

2)no enough Ab secondary invasion ..sever symptom

Clinical picture / 4 stage

A Prodromal Stage An Acute encephalitic Stage The Convalescence Stage A Sequela Stage …then death of the patient

Pathogenesis and immunity

Beside viral receptor, virus may attach to Fc receptor (receptor found on the

surface of macrophages and monocytes) via Ab to result in an increase of virus infection.(virus entry to inside the cell)

Antibody is produced to block infection, so if we have good a mount of Ab's to have a neutralization rxn( (binding of the virus with Ab ,so the virus will not be able to bind to the host cell)) However, non-neutralizing Ab may have antibody dependent enhancement (ADE) effect to enhance virus replication by hundred folds.


Arthropod-Borne Viruses

a) Dengue fever b) Yellow fever C)chikungunya

signs and symptom

Fever/Rash/Arthritis

Triad of fever/rash/arthritis

Symptoms generally appear after 2-3 days incubation

a) fever, chills, myalgia

b) polyarthralgia mainly affecting small joint

c) maculopapular rash

Arthritis generally resolves in a few weeks, but may persist for months, or years in some cases.

Encephalitis

Don’t remember the name in the slide

In Encephalitis we need a vector ,a reservoir (animal ), u need human

Vector transmitted virus from animal to human (host )

West Nile Virus

Geographic distribution :

Africa, Middle East, Western Asia, Europe, Australia, North America, Central America

Principal arthropod vector – mosquitoes

Primary host – wild birds

Flavivirus


It causes encephalitis which has Case-fatality rates average 10 – 20 % (higher in

elderly).death or Survivors may be left with permanent neurologic sequelae such as mental retardation, epilepsy, paralysis, deafness, and blindness.

Diagnosis-:

++material of epdimology :we take it from human ,vector ,suspected animal

Laboratory Tests++

*Tentative diagnosis

*Antibody titer:we can use serelogical exam to look for Ab titer

*JE-specific IgM in serum or CSF in encephalitis

*Definitive diagnosis if we can isolate the virus

*Virus isolation: Blood, CSF sample, brain

So we can do:

1 )serological exam

2)culture

3 )direct detection test:- by doing molecular biology to look for RNA of the specimen or direct detection of Ag in the infected cells (virus enter macrophage

and make new antigenicity to the cell so we make direct to look for new Ag.

Prevention :Because the vector are the main things if we can protect our self from the vector this mean we can prevent the transmition

Method for prevention:


Surveillance - of disease and vector populations( the first thing they do in malaria prevention is killing the mosquito in order to get ride off the disease'

Control of vector - pesticides, elimination of breeding grounds

Personal protection - screening of houses, bed nets, insect repellants

Vaccination - available for a number of arboviral infections e.g. Yellow fever, Japanese encephalitis, Russian tick-borne encephalitis

Treatment/Vaccines/Control measures :

A. Encephalitis

1 .Vaccines exist for a number of these viruses, but are used mainly for horses, at risk lab workers, and some fowl known to be intermediate hosts

2 .Control of mosquitoes is major countermeasure.

B. Yellow Fever: Live attenuated virus vaccine. Used when going to endemic areas

If we have break any of these (host ,virus ,vector) so you prevent the

cycle of infection.

Arboviruses

Positive sense ssRNA genome, icosahedral nucleocapsid, envelopedPathogenesis

Structure


Transmitted by bite of insect from host species; sylvan and urban cycles

Replication in cytoplasm; budding Viremia to target tissue

Influenza-like initial symptoms; different viruses cause encephalitis, hemorrhagic fever, hepatitis, rash, arthritis

Pathogenesis

Serology and nucleic acidDiagnosis

No human vaccines except for Yellow Fever live attenuated vaccine, control of insect population

Treatment/prevention

GENERAL HISTORY OF RETRO VIRUS

1960 :The name of retroviruses came from Howard Temin who is the first one discovered the( reverse transferees) in bacteria and has the nobal prize in 1990.

1980 :Human T-cell leukemia virus discovered, the first pathogenic human retrovirus.

1982 :Human immunodeficiency virus discovered, But actually it is not discovered at that time but the up normal clinical picture it was seen at that time

1990 :First gene therapy trial involving the use of retroviral-based vectors (they take the gene responsible for production ADA and attach it with the RNA of retrovirus and inject it in the host cell )which is a patient with a deficiency in adenosine deaminase (ADA)so he well be able to produce it

2006 :Xenotropic murine leukemia-related virus discovered.

Retroviruses

Retro virus from it is name it is ( DNA….RNA…Protein) virus.

Unique replication cycle based on reverse transcription ;Flow of information from RNA to DNA

Retroviruses cause tumor to their original host cell&they have been isolated from numerous species including chickens (RSV), mice (MLV), monkeys (SIV), and humans (HIV, HTLV).


Type of retrovirus

*Simple Retroviruses: it contain at least 3 main gen group which needed for synthesize virus.(we well talk about it ).

*Complex retrovirus : composed of 3 gen found in simple virus in addition to anther gen

How they infect the cell??

Reteovirus envelope so it has to attach to the membrane receptor of the host cell and they enter to the cell and infect it .

One IMP thing about it :we know in Tumor production we have something called oncogen .

Oncogen first time discovered in retroviruses and these virus sometime we call it retrovirus oncogen..(if mutation occur in the original virus they become oncogen and cause tumor viruses )

THE OLD NOMENCLATURE// Members(groups):

1- Oncogenic viruses (Oncoviruses) (endogenous)

Avian oncoviruses: RSV, AMV, AEV

Murine oncoviruses: e.g., MoMLV, A-MuLV.

Mammalian oncoviruses: e.g., FeLV, HaMSV, SSV.

Mouse Mammary Tumor Virus (MMTV)

Mason-Pfizer Monkey Virus (MPMV

Human T-Cell Lymph tropic Virus

2- Lentiviruses – HIV-1, HIV-2(associated with “slow” diseases or those with long latent periods)

3- Spumaviruses – mainly in monkey(“foamy” viruses named because of the pathogenic change observed I infected cell )


Slide 50: dr mention one example on

simple virus: Alpharetrovirus( Avian leukemia virus )

And complex virus : Deltaretrovirus(Human T-cell leukemia virus)

General feature for retrovirus

1-Enveloped virus with lipid bilayer and viral spike glycoproteins

2-Have outer matrix protein and inner core capsid containing viral genome

3-Genome: Two copies of single stranded positive-stranded(+ RNA)

4-All retroviruses contain gag, pol and env genes.

5-Simple – only gag, pol, env,Complex – additional genes involved in replication

6-All of them have Reverse transcriptase to generate DNA

7-Viral genes are integrated into host genome.

8-Progeny virus produced using host cell transcriptional and translational machinery which meen it well stop the cellular function of the host cell and turn it to viral ccc.

Retrovirus Genome (Diploid)


Retrovirus genome is +RNA ,Ranges from 7-10 kb in size (1 copy) Diploid: 2 copies/virion, Important in high recombination rate So their antigencty not

stable &always there is change .

This gag(group spasific antigen,pol(polymerase enzyme), env(envelope) ) gene of simple virus

In complex we can add another gen:

MA-Matrix, CA- Capsid , NC- Nucleocapsid

In other we can add:

SU- surface envelope protein, TM- transmembrane envelope protein

in addition it can produce:

PRO- Protease, RT- Reverse transcriptase ,IN- Integrase

Viral life cycles

There is :


Virulent – these viruses lyse (kill) their host cell after infection. RapidTemperate – these viruses can replicate their genome along with the host cell genome without killing the host cell.but if anything activated the cell the virus start to develop very rapidly it can be induced by IL,infection,drug And capable of lyzing the host cell.need along time

Distinct Steps in the Retroviral Life Cycle/look to icture

1st step :Attachment, Fusion, and Entry

2nd step :Reverse Transcription

3rd step :Integration

4th step:Transcription

5th step :Translation

6th step :Assembly, Budding, and Maturation


DONE BY JUMANA MANSOUR AL-ZOUBI

BEST OF LUCK

SORRY FOR AN ANY MISTACKES

SPECIAL THANX TO MY SISTER NARIMAN

web viewstructure of virus itself ... ( avian leukemia virus ) and . complex virus : deltaretrovirus...

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