02 February 2009

Retrovirus and Flaviviridae

For Microbiology B which is my year 1 semester 2 module, two topics i have learnt about is called Retrovirus and Flaviviridae.
Most of what I have learnt about Retrovirus is mainly:
2 types of Retroviruses:
• Deltaretrovirus
• Lentivirus
The properties of Retroviruses
• Spherical enveloped virion (A complete virus particle)
• 80 – 100nm
• Ribonucleoprotein in central nucleoid (concentric or truncated cone in lentivirus) within icosahedral capsid
• Envelope with glycoprotein peplomers (a glycoprotein structural unit found in the lipoprotein envelope of enveloped viruses)
• Reversed transcriptase
- Genome doesn’t serve as mRNA
• 2 copies of linear positive sense single stranded RNA
- 7-10kb long
• 3’ polyadenylated tail (protects the mRNA from digestion with nuclease and greatly increases the efficiency of translation)
• 5’ cap (specially altered nucleotide end to the 5' end of precursor messenger RNA)
- The process of 5' capping is vital to creating mature messenger RNA which is then able to undergo translation. Capping ensures that the messenger RNA is stable while it undergoes translation in the process of protein synthesis. It is a highly regulated process, which occurs in the nucleus
• Formation of long terminal repeats before provirus DNA inserted into host genome
gag, pol, env genes some regulatory genes, some oncogenes
- gag
• Group-specific antigen
• Virion core (capsid protein)
- pol
• Polymerase (reverse transcriptase)
• RNase H (part of the viral reverse transcriptase enzyme, it is absolutely necessary for the proliferation)
- env
• envelope
Types of Retroviruses
• Tumour-forming
- Trans-activating (HTLV)
• Non-tumour-forming
- HIV

HTLV-1
The image below shows the infection and life cycle of what a HTLV-1 virus goes through.

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http://www.ambion.com/tools/pathway/loadImage.php?pos=br&im=images/Cellular%20Transformation%20by%20HTLV1.jpg

• Adult T-cell leukemia/lymphoma (ATLL)
- Acute aggressive leukemia resulting in death in 12 months
- No known cure yet
• Tropical spastic paraparesis / HTLV-1 associated myelopathy
- Wasting of neurons (lost of myelin sheaf)
- Back pain followed by paralysis

HIV
The image below show the infection and life cycle of what a HIV virus goes through.

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http://www.nwabr.org/education/pdfs/hiv_lifecycle.jpg

This is a video illustrating the infection and a life cycle of the HIV virus.



This picture illustrates the pathogenesis of HIV.

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Primary Infection
Acute Stage
• Flu-like Symptoms
• Fever
• Skin Rash
• Swollen Lymph nodes
- Virulence factors (degree of pathogenicity of an organism, the relative ability of a pathogen to cause disease)
• Rate of replication
• Propensity to mutate
• Cytopathogenicity (the production of pathological changes in cells)
- Host resistance
• Suppression by CD8 T suppressor cells
• Presence of cytotoxic T-lymphocytes
Asymptomatic Stage
• Fatigue
• Depression
• Weight loss
• Memory disorder
- No apparent disease
- Fall in CD4 T-lymphocytes (primary target cells)
Symptomatic Stage
• AIDS-related complex
- Diseases not considered definitive of AIDS
- May be attributed to HIV infection
- Indicative of defect in cell-mediate immunity
• AIDS
- Opportunistic infections as a result of fall in CD4 T-lymphocytes
AIDS Therapy
• Non-specific therapeutic management
- To boost general health
- Vitamin
- Minerals
- Anti-oxidants
• Specific therapeutic management: antiretroviral therapy
- Nucleoside Reverse Transcriptase Inhibitors
• AZT (azidothymidine)
• 3TC (lamivudine)
- Non-nucleoside Reverse Transcriptase Inhibitors
• Efavirenz
• Nevirapine
- Protease inhibitors
• Indinavir
• Ritonavir
- Rapid mutations due to inefficiency of reverse transcriptase
- Combination therapy to combat resistance

CLICK PICTURE FOR LARGER VIEW! :D

• Immunomodulation
- Enhancement of immune system through treatment with:
- Interleukin-2 (still under study)
• Vaccines
- Many candidates under development and trials
- None so far proven useful
That's my knowledge of Retroviruses.

Here's a picture of AIDS Awareness just for the fun of it:

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Flaviviridae
Most of what I have learnt about Flaviviridae is mainly:
Two types of viruses:
• Flavivirus
- Yellow Fever
- Dengue
- West Nile
• Hepacivirus
- Hepatitis C
The properties of Flaviviridae
• Spherical enveloped virion (A complete virus particle)
• 40 – 50nm
• Inner core protein C
• Membrane / matrix protein M
• Envelope with glycoprotein peplomers (E)
• Single linear 11kb positive sense single stranded RNA
- Infectious mRNA
• 3’ polyadenylated tail (protects the mRNA from digestion with nuclease and greatly increases the efficiency of translation)
• 5’ cap (specially altered nucleotide end to the 5' end of precursor messenger RNA)
- The process of 5' capping is vital to creating mature messenger RNA which is then able to undergo translation. Capping ensures that the messenger RNA is stable while it undergoes translation in the process of protein synthesis. It is a highly regulated process, which occurs in the nucleus
• Cytoplasmic replication (perinuclear)
• Polyprotein from genomic RNA cleaved
• 3 structural proteins
• Several non-structural proteins
The image below shows how the strain of flaviviridae virus is passed.

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http://www.microbeworld.org/images/scientists/interviews/arbocycle.jpg

Dengue
The image below shows the infection and life cycle of what a Dengue virus goes through.

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http://www.klinikum.uni-heidelberg.de/typo3temp/pics/e102b53902.gif

Dengue
• Most important type of arbovirus presently
• Range which infection is prominent in is, Southeast Asia, America, Pacific regions and Africa.
• Two types of signs in which dengue causes:
- Non-fatal dengue fever (DF)
- Fatal dengue haemorrhagic fever(DHF) / Dengue shock syndrome (DSS)
• 4 distinct serotypes based on neutralization test:
- DEN-1
- DEN-2 (shows greatest antigenic and genotypic distance from the others)
- DEN-3
- DEN-4
• Protective immunity after infection homotypic
Symptoms of dengue fever
• Many infections are asymptomatic
• Acute infection:
- Fever
- Severe headache (frontal)
- Retro-orbital pain
- Nausea
- Vomiting
• Severe muscle and bone pain
• Severe arthralgia (joint swelling, mainly the back) which is also known as the break bone fever
• Maculopapular rash just before recovery
Picture of maculopapular rash:

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http://www.pedrheumonlinejournal.org/nov-dec/Images/figure2.jpg

Dengue Haemorrhagic Fever (DHF) / Dengue Shock Syndrome (DSS)
Key factors of DHF and DSS:
• Prior infection
• Age (seldom occurs in individuals above the age of 15)
Similar to Yellow Fever in biphasic nature (having two phases):
• Initial symptoms similar to DF but then it is followed by remission (a complete or partial disappearance of the signs and symptoms)
• Sudden deterioration of patient condition
Symptoms of DHF / DSS
• Severe prostration
• Hypotension
• Circulatory collapse
• Bleeding
- Petechiae in skin, mucous membranes (mouth) [a small (1-2mm) red or purple spot on the body, caused by a minor haemorrhage]
- Injection and punction sites
- Gastrointestinal bleeding
- Haemorrhagic pneumonia
• Shock

World Health Organisation (WHO) Grading of DHF:
• GRADE 1 (Fever with non-specific, constitutional symptoms and haemorrhagic manifestations being a positive tournique test)
• GRADE 2 (Fever with non-specific, constitutional symptoms and specific haemorrhagic manifestations)
• GRADE 3 (Signs of circulatory failure and hypotension)
• GRADE 4 (Profound shick with pulse and blood pressure undetectable)

This picture illustrates the possible pathogenesis of DHF/DSS.

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http://www.umassmed.edu/cidvr/graphics/rothman.gif

Pathogenesis of DHF / DSS
Not well understood despite intensive studies
2 types of theories:
• Virulent strain theory
- Some strains are more virulent than others
- Molecular studies shows variations in sequences amongst different strains within serotypes
- Early evidence pointed to DEN-2
• Antibody enhancement
- Main theory for DHF / DSS
- Main cell target of dengue: Monocytes or macrophages
- Most cases of DHF / DSS had prior infection of in infants below 1 year had material Ab
- Experiments on monkeys showed similar enhancement.
• Possible causes of DHF / DSS
- Immune system overreacting
- Severe Acute Respiratory Syndrome
Control of dengue:
1. Insecticide
2. Mosquito screen
3. Remove stagnant water

Yellow Fever
The image below shows the infection and life cycle of what a Yellow Fever virus goes through.

CLICK PICTURE FOR LARGER VIEW! :D
http://jvi.asm.org/content/vol81/issue17/images/large/zjv0170795060001.jpeg

Yellow Fever
Tropical disease in Latin America and Africa
Incubation period: 3–6 days
Symptoms of Yellow Fever:
• Viraemia
• Infectious
• Headache
• Malaise
• Nausea
• Lassitude
• Muscle ache (3days)
• Flushing of head and neck
• Conjunctival injection
• Strawberry tongue
Symptoms of Severe Yellow Fever:
• Remission after acute yellow fever
• Haemorrhagic, hepatic and renal disease
• Fever
• Vomiting
• Abdominal pain
• Dehydration
• Prostration
• Haemorrhagic/coffee-ground diathesis(black vomit)
• Bleeding from puncture site of injections and drip needles
• Jaundice
• Massive haematemesis/haemoptysis/intra-abdominal bleeding
• Renal failure
• Hypotension
• Shock
Virus absent from blood, but antibody titre is high – implying autoimmunity may play a major role
Mortality 20–50%
Survivors suffers from extended chronic jaundice before full recovery, hepatic and renal failure may persist

Control of dengue:
1. Insecticide
2. Mosquito screen
3. Remove stagnant water
4. Attenuated vaccine

West Nile Fever
The picture below shows the west nile virus transmission cycle

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http://dittamore.us/images/west_20nile_20virus_20life_20cycle.gif

West Nile Fever
Common disease in Africa, West Asia, Europe and Middle East
Epidemic in US in 2002
Symptoms of West Nile Fever
• Mainly mild to no symptoms
• Fever
• Headache, body aches
• Skin rash
• Swollen lymph glands
Severe symptoms of West Nile Fever (mainly in people aged 50 years and above)
• Crossing blood-brain barrier
• Encephalitis
• Meningitis
Control of dengue:
1. Insecticide
2. Mosquito screen
3. Remove stagnant water