Friday, January 9, 2009

Retroviridae and Flaviviridae

Retroviridae

Introduction to Retroviruses
Retroviruses are viruses that are capable of using reverse transcription of viral RNA into DNA during replication. Human Immunodeficiency Virus (HIV) is one of the members of this family. Another member is feline leukemia. In 1908, retroviruses were found by Vilhelm Ellermann and Oluf Bang. Animal infection and disease were the focus of study of retroviruses for the first sixty years. Then, in the 1960s and 1970s, viral replication cycle and pathogenic effects at the cellular level were the focus of study. Today, the diverse pathogenic effects of these viruses at the cellular and modular level are the focuses of the study.

History of Retroviruses
Chicken sarcoma, a disease caused by a virus, was uncovered by Peyton Rous in 1911. In 1966, he won the Nobel Prize. In 1970, Howard Temin and David Baltimore found the reverse transcriptase enzyme separately, and they won the 1975 Nobel Prize. In 1989, Michael Bishop and Harold Varmus won the Nobel Prize for discovering the oncogenes and the role of oncogenic viruses and cancer. In 1980, Robert Gallo and his team found the first human retrovirus that resulted in adult T cell leukemia. In 1984, Luc Montagnier found out the agent that caused AIDS and it was confirmed by Gallo.

The Genera of Retroviruses


  • Retroviridae (family)
  • Orthoretrovirinae (sub family)
    - Alpharetroviruses
    - Betaretroviruses
    - Gammaretroviruses
    - Deltaretroviruses
    - Epsilonretroviruses
    - Lentivirus
  • Spumaretrovirinae (sub family)
    - Spumaretrovirus
Genome Structure of a Retroviridae
Retroviridae has a positive sense, single-stranded RNA and is linear. It has 3’ polyadenylated tail and 5’ cap. They have reverse transcriptase and they form long terminal repeats before inserting provirus DNA into the host genome.

Virion Structure of a Retroviridae
An envelope, a nucleocapsid and a nucleoid can be found in the virions of a retroviridae.Retroviruses have spherical enveloped virions to pleomorphic enveloped virions which are measured 80nm to 100nm in diameter. Within the icosahedral capsid, it has a central nucleoid that consists of ribonucleoprotein. The nucleoid is either concentric or truncated cone in lentiviruses. The capsid is enveloped with glycoprotein peplomers.





Reproduction Cycle of a Retroviridae in a Host Cell
The virions of a retroviridae interact between a virally-encoded enveloped protein and a cellular receptor and then enter the host cells. The enzyme reverse transcriptase which is present in the virion transcribed viral RNA into DNA copy. The viral DNA copy merges and becomes a permanent part in the host genome. Provirus is referred to this merged DNA. The viral genes are being expressed using the host cell’s transcriptional and translational machinery. To create new viral RNA, the provirus is being transcribed by the host RNA polymerase II. Other cellular processes then transported this new viral RNA out of the nucleus. Some of the new RNAs are being divided to enable the expression of some genes, and those undivided new RNAs are left as full-lengths RNA. The host cell’s translational machinery combines the viral proteins. The viral proteins then gather and sprout from the host cell. All members of the retroviridae go through this reproduction cycle except for spumaviruses. The reverse transcription is completed by the spumaviruses in the virus-producing cells, instead of the infected target cells. DNA genome is found in the infectious virus.




Human T-lymphotropic virus 1 (HTLV-1)
HTLV-1 is a retrovirus that forms tumour and has infected 10 to 20 million of people worldwide. It is considered the first retrovirus that causes Adult T-cell leukemia (ATL). Perinatal transmission by blood or breast milk, sexual contact, or exposure to contaminated blood products can cause ATL. Acute aggressive leukemia can lead to death in a year, and here is no cure to it yet. HTLV-1 also causes Tropical Spastic Para paresis. Neurons are wasted and back pain occurs, which then leads to paralysis.

Human Immunodeficiency Virus (HIV)
Acquired Immunodeficiency Syndrome (AIDS) is caused by HIV. AIDS can be transmitted via sexual contact and any form of contacts with blood. Mother passes the AIDS disease to the child via placenta, mucosa and breast milk. AIDS is being spread worldwide.




Pathogenesis of HIV

Primary Infection

Primary infection is the acute stage whereby the symptoms of it are flu-like symptoms, fever, skin rash and swollen lymph nodes.

Asymptomatic Stage
At this stage, there is no visible disease, but there is a fall in CD4 T-lymphocytes, a primary target cell.
The possible symptoms for this stage are tiredness, depression, loss of weight and memory disorders.


Symptomatic Stage
This is the stage where there is AIDS –related complex. The diseases are not really considered as ADIS, but may lead to HIV infection. This indicates the defect in cell-mediate immunity. When there is a fall in CD4 T lymphocytes, opportunistic infections occur which will then lead to AIDS.

AIDS Therapy
There are four types of AIDS therapy.
1. Non-specific therapeutic management
2. Specific therapeutic management
3. Immunomodulation
4. Vaccines



Non-specific therapeutic management
This therapy helps to boost the general health through the intake of vitamins, minerals, anti-oxidants and many others.

Specific Therapeutic Management
One of the specific therapeutic management is through antiretroviral therapy. There are three types of inhibitors – the nucleoside reverse transcriptase inhibitors, the non- nucleoside reverse transcriptase inhibitors and the protease inhibitors. Azidothymidine (AZT) and lamivudine (3TC) are examples of nucleoside reverse transcriptase inhibitors. Efavirenz and nevirapine are examples of non-nucleoside reverse transcriptase inhibitors. Indinavir and ritonavir are examples of protease inhibitors. The inefficiency of the reverse transcriptase leads to rapid mutations. Hence, to overcome this resistance, there is a need to combine therapy.

Immunomodulation
This therapy is still under study. However, there is an improvement of immune system via treatment with interleukin-2.

Vaccines
Many people are still undergoing development and trails, but so far, none of it are being proved to be useful.


References
http://microbewiki.kenyon.edu/index.php/Retroviridae
http://diverge.hunter.cuny.edu/~weigang/Images/13-19_retroviridae_1.jpg
http://www.stanford.edu/group/virus/retro/2000/retroheader.jpg
http://microbewiki.kenyon.edu/index.php/Human_T-lymphotropic_virus_1
http://www.tthhivclinic.com/fig_3.gif

Flaviviridae

Introduction to Flaviviridae
Arboviruses (arthropod-borne viruses) are viruses that are transmitted by the bite of an arthropod vector. The viruses tend to multiply in the bodies of an arthropod. Alphaviruses and Flaviviruses are the two common types of Arboviruses. Alphaviruses belong to a family, named Togaviridae, and Flaviviruses belong to a family, named Flavivridae. Flaviviridae is a family name and its name came from a type virus of Flaviviridae, known as the Yellow Fever virus. In Latin, flavus means yellow.

A lot of viruses that cause diseases in humans are found in Flaviviridae. A total of 69 pathogens can be found in Flaviviridae. The genus of the Flavivirus consists of many injurious creatures, and this includes the yellow fever virus, the dengue fever virus and the West Nile virus. Hepacivirus genus has hepatitis C virus and its relatives.

Genome Structure of Flaviviridae
The genome of Flaviviridae consists of a linear, positive-sense, single stranded RNA, and the genome is not segmented. The genome has a 5’-end carries a methylated nucleotide cap or genome-linked protein. It also has a 3’ polyadenylated tail, polyprotein from genomic RNA cleaved, 3 structural protein and some non-structural proteins. The genome undergoes cytoplamsic replication.

Virion Structure of Flaviviridae
The virions of the Flaviviridae are spherical to pleomorphic and the virions are enveloped. The virions are measured 40nm to 50nm in diameter. An envelope and a nucleocapsid are present in the virions of Flaviviridae. The capsid is enveloped with glycoprotein peplomers. The surface projections of the capids are made up of small spikes that are surrounded by a prominent fringe. The capsid has a polyhedral symmetry and it is round. The capsid has an inner core protein. The core is measured 20nm to 30nm in diameter, and it is isometric.




Dengue
Dengue is currently the most important arbovirus, and the chances of getting dengue is higher in Southeast Asia, America, Pacific and Africa. Dengue Fever is not a deadly disease. The deadly dengue viruses are Dengue Haemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS).

Dengue has four different serotypes, and the serotypes are based on neutralisation test. There are DEN-1, DEN-2, DEN-3 and DEN-4. Among the four serotypes, DEN-2 displays the greatest antigenic and genotypic distance. After infection homotypic, it produces a protective immunity.




Dengue fever
An illness that is caused by infection with a virus which is transmitted by the Aedes mosquito is known as Dengue Fever. The virus enters the body’s glands when a mosquito, which carries the virus, bites a person. The virus multiplies in the glands and it enters the bloodstream. Dengue fever is not contagious.

The infections of dengue fever are asymptomatic. Fever, severe headache, retro-orbital pain, nausea and vomiting are the results of an acute infection. Symptoms also include severe muscle and joint pain, lower back pain and flushed face. These symptoms last for two to three days. The patient will then experience heavy sweats when the fever drops. The temperature will rise again after the patient feels better after one day. Rashes and headache will also occur. The symptoms normally last till a maximum of ten days. Patient will feel weak and tired for a maximum of one month afterwards. Dengue Haemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS) are the severe cases f dengue fever.




Dengue Haemorrhagic Fever / Dengue Shock Syndrome
Dengue Haemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) normally occur in individuals that are above the age of 15. The biphasic nature of DHF and DSS are similar to yellow fever. DHF and DSS cause fever, headache and cough. The virus causes the swelling and leaking of blood vessels and petechiae is formed. Petechiae are small purple spots found on the skin. The area, in which the bleeding is worse, is shown by the bruised skin. Severe abdominal pains and vomiting of coffee grounds diathesis are the results of gastrointestinal bleeding. When the blood runs out of clotting factors, haemorrhaging occurs. The damaged blood vessels cannot supply the required blood flow and the oxygen it carries to the body’s tissues, when the damaged blood vessels enlarge. This eventually leads to shock which major organs, such as the heart and the kidneys, can be damaged.

Pathogenesis of DHF and DSS
There are 2 theories – virulent strain theory and antibody enhancement. Based on the virulent strain theory, there are some strains which are more virulent than the others. Among the different strains within the serotypes, there are variations in the sequences. This is shown by the molecular studies. Den-2 has been proven by the early evidence.

The antibody enhancement is the main theory for DHF and DSS. Monocytes or macrophages are the main cell target of DEN. Prior infection can be found in most cases of DHF and DSS, or even infants below the age of one had maternal antibody. Similar enhancement had been proven in monkey experiments.

Overreacting of Immune System and Severe Acute Respiratory Syndrome are the possible causes of DHF and DSS.


Control of Dengue
There is no vaccination for dengue. Hence, dengue can only be minimized and controlled by:


  • Insecticide
  • Mosquito screen
  • Removal of stagnant water
Grading of DHF
Grading of DHF is done by WHO, and there are four grade – Grade I, Grade II, Grade III and Grade IV. Fever that is not specific and with constitutional symptoms and the only haemorrhagic proof being a positive tourniquet test are being classified under Grade I.


Grade II is similar to Grade I, but Grade II has specific haemorrhagic manifestations. Signs of circulatory failure or hypertension are graded under Grade III, and lastly, profound shock with pulse and blood pressure that is undetectable is under Grade IV.

Yellow Fever
Yellow fever is a severe viral infection. Yellow fever is transmitted by mosquito, and it is common is tropical areas. Hepatitis is the classic feature of yellow fever. This is also the reason for the yellowing of skin, known as the jaundice.

Symptoms of Yellow Fever
From infection to developing yellow fever, the incubation period is 3 to 6 days. In acute infection, headache, malaise, nausea, lassitude, muscle ache, flushing of head and neck, conjunctival injection and strawberry tongue are the symptoms. There is a remission after acute yellow fever. In severe cases, fever, vomiting, abdominal pain, dehydration, prostration, haemorrhagic, coffee-ground diathesis, and bleeding from puncture sites of injections and drip needles occur. In addition, jaundice, massive haematemesis, haemoptysis, intra-abdominal bleeding, renal failure, hypertension, and shock also occur. Though virus is not present in the blood, antibody titre is still high,. This implies that the autoimmunity may play an important role.

Severe yellow fever resulted in 20% to 50% death rate. Before full recovery, survivors suffered from extended chronic jaundice. Also, renal failure and hepatic may continue.

Control of Yellow Fever
Yellow fever can be controlled by attenuated vaccine. It can also be controlled and minimized by:

  • Insecticide
  • Mosquito screen
  • Removal of stagnant water


West Nile Fever
West Nile Fever is a virus and it comes from a family, called Flaviviridae. West Nile Fever can be found in the tropical areas, as well as temperate areas. West Nile Fever infects mainly the birds, although it is known to infect humans and animals, such as dogs, cats, horses, domestic rabbits and squirrels. Human is infected through the bite of an infected mosquito. West Nile Fever occurs mainly in individuals who are above the age of 50.

History of West Nile Virus
West Nile Virus originated from Uganda and was found out in 1937. West Nile Virus is common in Africa, West Asia, Europe and Middle East. In 1999, West Nile Virus spread through US, New York, and was epidemic in 2002.

Symptoms of West Nile Fever
West Nile Fever has mild or no symptoms. In mild symptoms, fever, headache, body aches, skin rash and swollen lymph glands are the results of it. In severe symptoms, crossing of blood-brain barrier, encephalitis and meningitis are the results.

Control of West Nile Fever
West Nile Fever can be controlled or minimized by:

  • Insecticide
  • Mosquito screen
  • Removal of stagnant water
References
http://microbewiki.kenyon.edu/index.php/Flaviviridae
http://www.triroc.com/sunnen/images/icosahedral337x446.gif
http://media-files.gather.com/images/d209/d946/d743/d224/d96/f3/full.jpg
http://www.lapublichealth.org/acd/images/WnvCycle.gif
http://images.google.com.sg/imgres?imgurl=http://media-files.gather.com/images/d209/d946/d743/d224/d96/f3/full.jpg&imgrefurl=http://www.gather.com/viewArticle.jsp%3FarticleId%3D281474976828599&usg=__Pquq8Gm5NxduCfmqgS4YmWUOECM=&h=367&w=550&sz=30&hl=en&start=7&um=1&tbnid=vPXPB_pO4_NrTM:&tbnh=89&tbnw=133&prev=/images%3Fq%3Ddengue%2Bfever%26um%3D1%26hl%3Den%26sa%3DN
http://www.netdoctor.co.uk/infections/yellowfever.htm
http://en.wikipedia.org/wiki/West_Nile_virus
http://www.ocvcd.org/images/wnv1_clip_image002.jpg

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