Emerging Viruses

Viruses are obligate parasite that have no known value to man. Viruses have been around for a long time in many species and most of them emergent are zoonotic.

What causes viruses to emerge, as scientificaly study, most implortant factor of emerging viruses is human behaviour. Which virus are bound to spontaneous evolution of a new virus entity.

Emerging virus frm last 6 years:

Now= 1)Dengue virus (Flavivirus)
2)Influenza vitus(Orthomyxovirus)

Nov 2002-July 2003= SARS (Coronavirus)

Sep 1998-April 1991= Nipah virus (Paramyxovirus)

EG of emerging virus: Influenza virus

How avian influenza mutate........
H3N2 infect man, H5N1 infect birds, H5 is efficient at attachment so when Co-infection of both happen and in the host the virus replicate itself this process is call Random reassortment where the RNA strands transcribed and a new viral protein synthized thus with the mix, a ''new influenza virion formed, the H5N2.

So what are these H and N stand for...

H stand for Hemagglutinin
N stand for Neuraminidase

and there are 16 type of H and 9 type of N..some example of random assortment are H1N1 and H3N2

Flaviviridae

The Flaviviridae are a family of viruses that are primarily spread through arthropod vectors (like ticks and mosquitoes).

The family gets its name from Yellow Fever virus, a type virus of Flaviviridae.
(Yellow fever was in turn named as it can cause jaundice in victims.)

PROPERTIES

Flaviviridae have monopartite, linear, single-stranded RNA genomes of positive polarity, 9.6- to 12.3-kb in length.

The 5'-termini of flaviviruses carry a methylated nucleotide cap, while other members of this family are uncapped and encode an internal ribosome entry site.
Virus particles are enveloped and spherical, about 40-60 nm in diameter.

Major diseases caused by the Flaviviridae family include:
Dengue fever
Yellow fever
West Nile fever

Dengue fever

The virus that causes dengue fever is called an arbovirus, which stands for arthropod-borne virus. Mosquitoes are a type of arthropod.

Symptoms

This is manifested by a sudden onset of severe headache, muscle and joint pains, fever and rash. The dengue rash is characteristically bright red petechiae and usually appears first on the lower limbs and the chest. In some patients, it spreads to cover most of the body. There may also be gastritis with some combination of associated abdominal pain, nausea, vomiting or diarrhea.

Much milder symptoms which can be misdiagnosed as influenza or other viral infection when no rash is present.

Treatment

The mainstay of treatment is timely supportive therapy to tackle shock due to haemoconcentration and bleeding. Close monitoring of vital signs in critical period is vital.
Increased oral fluid intake is recommended to prevent dehydration.

Prevention
Vaccine development
Mosquito control

West Nile fever

The West Nile virus is also an arbovirus. It can cause infections in animals and humans; in some cases, the infections can lead to fatal meningitis or encephalitis, which are inflammations of the spinal cord and brain. It is is transmitted by a culex mosquito.

In many cases, it can be a serious illness that generally affects the central nervous system, leading to a variety of symptoms that differ from person to person. It is not contagious by touch, but can be spread by infected mosquitoes, transfusions, transplants, or from mother to child during pregnancy.

Symptoms

West Nile virus infections usually begin with flu-like symptoms. Only approximately one in 150 people infected will develop severe symptoms, including headaches, neck stiffness, disorientation, seizures, fever, numbness, paralysis, or muscle weakness. In the worst cases, infection with West Nile virus can lead to death or permanent disability.

There is no cure for West Nile virus infection once the infection occurs.

Yellow fever

The yellow refers to the jaundice symptoms that affect some patients. Yellow fever has been a source of several devastating epidemics and 300,000 people are believed to have died from yellow fever in Spain in the 19th century.

Pathogenesis

Yellow fever is caused by an arbovirus, a positive sense single-stranded RNA virus. Human infection begins after deposition of viral particles through the skin in infected arthropod saliva.

Following systemic lymphatic infection the virus proceeds to establish itself throughout organ systems, including the heart, kidneys, adrenal glands, and the parenchyma of the liver; high viral loads are also present in the blood.

Symptoms

In mild cases only fever and headache may be present.
The severe form of the disease commences with fever, chills, bleeding into the skin, rapid heartbeat, headache, back pains, and extreme prostration.
Nausea, vomiting, and constipation are common. Jaundice usually appears on the second or third day.

After the third day the symptoms recede, only to return with increased severity in the final stage, during which there is a marked tendency to hemorrhage internally; the characteristic “coffee ground” vomitus contains blood. The patient then lapses into delirium and coma, often followed by death.

During epidemics the fatality rate was often as high as 85%.

Prevention

In 1937, Max Theiler developed a safe and highly efficacious vaccine for yellow fever that gives a ten-year or more immunity from the virus. ((: Yays!

Treatment

There is no true cure for yellow fever, therefore vaccination is important. Treatment is symptomatic and supportive only.

-Gene Sia

Retroviridae

Host:
Virus infects vertebrates.

Description and Significance
A retrovirus is a genome virus that replicates by using a viral reverse transcriptase enzyme to transcribe its RNA into DNA in the host cell.
The DNA is then incorporated into the host's genome by an integrase enzyme.
The virus thereafter replicates as part of the host cell's DNA.

Genome Structure
The genome of retroviridae is dimeric, unsegmented and contains a single molecule of linear.
The genome is -RT and a positive-sense, single-stranded RNA.
Minor species of non-genomic nucleic acid are also found in virions.

Virion Structure
It consist of an envelope, a nucleocapsid and a nucleoid.
Spherical enveloped virion and measure 80-100 nm.
The virion RNA is 7 to 12 kb long, linear, single-stranded, non-segmented, and of positive polarity.

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When a retrovirus infects a cell:
- Its molecules of reverse transcriptase are carried into the cell attached to the viral RNA molecules.

- The reverse transcriptase synthesizes DNA copies of the RNA.

- These enter the nucleus and are inserted into the DNA of the host.

- These inserts are transcribed by the host's enzymes into fresh RNA molecules which re-enter the cytosol.

It injects its RNA into the cytoplasm of that cell along with the reverse transcriptase enzyme.

The cDNA produced from the RNA template contains the virally derived genetic instructions and allows infection of the host cell to proceed.

The virus that causes AIDS (Acquired Immune Deficiency Syndrome) is a retrovirus.

It is called HIV for human immunodeficiency virus.

Transmission

1.) Blood products

2.) Organ transplants

3.) Sexual intercourse

4.) Vertical Transmission

Clinical features

Primary infection

90% of patients develop a flu-like illness. Symptoms include, fever, night sweats, sore throat, lymphadenopathy, diarrhoea.

Asymptomatic phase

Of variable duration, from 2 to 10 years. Patients are clinically well, but infectious.

Prodromal phase

Insidious onset of a variety of prodromal disorders including weight loss, fever, persistant lymphadenopathy, oral candidiasis and diarrhoea. These symptoms precede the progression to AIDS.

Therapy

There is no effective vaccine available for HIV.

- Gene Sia

Poxiviridae

Taxonomic Structure of the Family

Family 00.058. Poxviridae
Subfamily 00.058.1. Chordopoxvirinae
Genus 00.058.1.01. Orthopoxvirus






At least 9 different poxviruses cause disease in humans, but variola virus (VV) and vaccinia are the best known.

VV strains are divided into

-variola major (25-30% fatalities) and
-variola minor (same symptoms but less than 1% death rate)

The precise origins of vaccinia virus are uncertain:

Edward Jenner, 14th May 1796, used cowpox to "vaccinate" 8 year old James Phipps, who he later challenged with VV and showed that he was protected.

For more than 100 years, the "vaccine strains" were propagated from arm-to-arm, but for at least the last 50 years, Vaccinia has been a distinct virus from cowpox.

Vaccination was almost universally adopted worldwide around 1800, but it took a major commitment from the WHO in 1965 to achieve eradication.

Eradication of smallpox was possible for 3 reasons:

1) There is no other reservoir for VV but man (including primates) (c.f. Arboviruses)

2) VV causes only acute infections, from which the infected person either:
a) dies
b) recovers with life-long immunity (c.f. Herpesviruses)

3) Vaccinia virus is an effective immunogen.



Infection with both viruses occurs naturally by the respiratory route and is systemic, producing a variety of symptoms, but most notably with VV characteristic pustules and scarring of the skin. Replication of vaccinia is more localized. Administration of vaccinia to immunocompromised hosts results in systemic infection with neurological damage or death. The vaccine is contraindicated in:

• Eczema, atopic dermatitis or other acute, chronic, or exfoliative skin conditions
• Diseases or treatments which cause immunodeficiency or immunosuppression
• Moderate or severe acute illnesses
• Previous allergic reaction to smallpox vaccine or any of the vaccine components
• Pregnancy
• Breastfeeding mothers


• Infants and children under 12 months of age

Clinical Virology – RNA viruses

Orthomyxoviridae and Picornaviridae

Unique features of RNA viruses
- Central Dogma
- DNA -> RNA -> Protein
- Infectious ( +RNA viruses)
- Unusual characteristic
- Distinguish between viral mRNA and host mRNA

Overview of Picornaviridae
There are 5 genera:
- Aphtoviru
- Cardiovirus
- Enterovirus
- Heptovirus
- Rhinovirus

Morphology
1. Virions (naked)
2. Nucleocapsid isometric
3. Incomplete or empty capsids common

Genome of Picornaviridae
1. Genome RNA is infectious
2. One linear (+) RNA
3. Long not translated region end of 5’ end ‘clover leaf’ structure (IRES)
4. Single polyprotein of 2100 – 2400 aa
5. Modified ends


Picornaviridae – Rhinovirus

Pathogenesis
1. Upper respiratory tract infection
2. 2 – 3 days incubation
3. Endogenous IFN helps
4. Synthesized IgA, titer decline with time
5. Serum IgA persists for years
6. Over 100 rhinoviruses

Symptoms
1. Watery nasal discharge
2. Congestion
3. Sneezing
4. Slight/No fever

Lab diagnosis
1. Virus culture
2. Nasal washing
3. EIA
4. PCR

Epidemiology
- Throughout the year
- A few serotypes circulating at the same time
- Nasal discharge contains a lot of virus

Control
1. No vaccine. Cause it can recover easily.
2. Observe personal hygiene. Example: Wash hands; do not touch nose/eyes.
3. Sneeze onto tissue and throw away
4. Avoid people having cold, and stay home when with cold.

History of virus
1. 430B.C first report of influenza epidemic –Athens
2. 1918 – Flu pandemic (25 – 40 million deaths!)
3. 1957 – 1958 and 1968-1969 epidemics.

But now, flu vaccine are available but very expensive!


Overview of Orthomyxoviridae
Morphology
1. Spherical in shape
2. Enveloped
3. Pleomorphic
4. Spikes on envelope
5. Groups of Hemagglutinin(HA) or Neuraminidase(NA)
6. Ratio of Hemagglutinin: Neuraminidase; 5:1


Genome
1. 8 segments in RNA, ss(-)
2. Each segment contains 3 polymerase polypeptides
3. 5’ and 3’ end of all segemtns highy conserved

Influenza Virus – Pathogenesis
1. Analogy of the Hemagglutinin for receptors in the epithelium causes respiratory tracts in human
2. Hereditary resistance
3. Immunocompromised
4. Existing antibodies includes Anti-HA Ab and IgA, IgG
5. Macrophages, NK cells, cytokines

Lab Diagnosis
1. Throat
2. Virus culture
3. Direct EIA
4. PCR

Epidemiology
1. Viral Incubation last 1 to 4 days
2. Few known serotypes circulating simultaneously
3. Virus abundant when being discharge through means of nasal

Antigenic
A mutation in the genetic code of surface antigen meant there is a Antigenic Drift whereas when gene reassort from different sub-types, it’s known as a Antigenic shift. Under the Antigenic drift, there are minor changes in the genome both in Influenza genome A and B. Antigenic drift happens all the time as it occurs as a point mutation thus resulting in a new strain that can be fatal and poses a threat to mankind. On the other hand, Antigenic shift does major changes in the genome resulting in gene reassortment and thus, creating a new subtype instead of a new strain. However antigenic shift only happens in Influenza genome A as well as the fact that it happens occasionally and not all the time.

Strain naming for Influenza is whereby the Influenza virus get recorded down as follow B/California/37/96 (H1N1). The B marks the genome of the influenza, whether it is A or B genome. Follow by location whereby the virus is isolated, as shown above, California. The number 37 marks the number of isolate and lastly the year of isolation which is 1996.

Control
Vaccines are common amount cases of preventing infection of influenza. However, it’s often useless because of the continuous Antigenic drift/shift that occurs in the genome of Influenza virus. Another way of controlling the virus is through usage of Antiviral drugs whereby attachment of the virus to the receptors are prevented. A few more examples are as follow, Transcriptase inhibitors, RT inhibitors, Protease inhibitors and lastly Assembly of virions.

Classification of Viruses

Viruses are classified into families, genera, and species. Based on the organisms they infect, the first broad division of viruses is into bacterial, plant, and animal viruses. Within these classes, other criteria for subdivision are used. Among these are general morphology envelope or the lack of it; nature of the genome (DNA or RNA); structure of the genome (single- or double-stranded, linear or circular, fragmented or non-fragmented); mechanisms of gene expression and virus replication (positive- or negative-strand RNA); serological relationship; host and tissue susceptibility; pathology (symptoms, type of disease).

The animal DNA viruses are divided into five families: Poxviridae, Herpesviridae, Adeno­viridae, Papovaviridae, and Parvoviridae. RNA animal viruses may be either single-stranded or double-stranded. The single-stranded are further subdivided into positive-strand and negative-strand RNA viruses, depending on whether the RNA contains the messenger RNA (mRNA) nucleotide sequence or its complement, respectively. Further, the RNA genes may be located on one or several RNA molecules (nonfragmented or fragmented genomes, respectively). The positive-strand RNA animal viruses contain six families: Picornaviridae, Calciviridae, Coronaviridae, Togaviridae, Retroviridae, and Nodamuraviridae. The nucleocapsid of negative-strand RNA animal viruses contains an RNA-dependent RNA polymerase required for the transcription of the negative strand into the positive mRNAs. Virion RNA is neither capped nor polyadenylated. The group is divided into five families: Arenaviridae, Orthomyxoviridae, Paramyxoviridae, Rhabdoviridae, and Bunyaviridae. The double-stranded RNA animal viruses contain only one group, the Reoviridae.

This following picture is the Baltimore Classification

I: Double-stranded DNA (Adenoviruses; Herpesviruses; Poxviruses, etc)

Some replicate in the nucleus e.g adenoviruses using cellular proteins. Poxviruses replicate in the cytoplasm and make their own enzymes for nucleic acid replication.

II: Single-stranded (+)sense DNA (Parvoviruses)

Replication occurs in the nucleus, involving the formation of a (-)sense strand, which serves as a template for (+)strand RNA and DNA synthesis.

III: Double-stranded RNA (Reoviruses; Birnaviruses)

These viruses have segmented genomes. Each genome segment is transcribed separately to produce monocistronic mRNAs.

IV: Single-stranded (+)sense RNA (Picornaviruses; Togaviruses, etc)

a) Polycistronic mRNA e.g. Picornaviruses; Hepatitis A. Genome RNA = mRNA. Means naked RNA is infectious, no virion particle associated polymerase. Translation results in the formation of a polyprotein product, which is subsequently cleaved to form the mature proteins.

b) Complex Transcription e.g. Togaviruses. Two or more rounds of translation are necessary to produce the genomic RNA.

V: Single-stranded (-)sense RNA (Orthomyxoviruses, Rhabdoviruses, etc)

Must have a virion particle RNA directed RNA polymerase.a) Segmented e.g. Orthomyxoviruses. First step in replication is transcription of the (-)sense RNA genome by the virion RNA-dependent RNA polymerase to produce monocistronic mRNAs, which also serve as the template for genome replication.b) Non-segmented e.g. Rhabdoviruses. Replication occurs as above and monocistronic mRNAs are produced.

VI: Single-stranded (+)sense RNA with DNA intermediate in life-cycle (Retroviruses)

Genome is (+)sense but unique among viruses in that it is DIPLOID, and does not serve as mRNA, but as a template for reverse transcription.

VII: Double-stranded DNA with RNA intermediate (Hepadnaviruses)

This group of viruses also relies on reverse transcription, but unlike the Retroviruses, this occurs inside the virus particle on maturation. On infection of a new cell, the first event to occur is repair of the gapped genome, followed by transcription.