About Viral Life Cycle

What is viral replication?
Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. For the virus, the purpose of viral replication is to allow production and survival of its kind. By generating abundant copies of its genome and packaging these copies into viruses, the virus is able to continue infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved.

Baltimore Classification
Viruses are classed into 7 types of genes, each of which have their own families of viruses, which in turn have differing replication strategies themselves. David Baltimore, a Nobel Prize-winning biologist, devised a system called the Baltimore Classification System to classify different viruses based on their unique replication strategy. There are seven different replication strategies based on this system (Baltimore Class I, II, III, IV, V, VI, VII).

Class I: double-stranded DNA (dsDNA)
- Replication exclusively nuclear; very dependent on host cell factors
- Replication in cytoplasm; viral genome contains all factors for genome replication and transcription
Examples: Herpes virus, pox virus, adenovirus

Class II: single-stranded DNA (ssDNA)
- Replication of genome in nucleus
- dsDNA formed to make new single-stranded daughters
- Extreme parasitism
Example: Parvoviridae

Class III: double-stranded RNA (dsRNA)
- Genome in several fragments
- Replication, transcription, translation regulated separately
- Monocistronic mRNA
- All activity in cytoplasm
Example: Reovirus

Class IV: single-stranded positive RNA [(+)ssRNA]
- Majority of animal and plant viruses
- Group 1 – polycistronic mRNA. Polyprotein formed and cleaved
- Group 2 – complex transcription process. 2 rounds of translation before formation of genomic RNA.
Examples: Hand food mouth disease, hepatitis A virus, hepatitis C virus

Class V: single-stranded negative RNA [(-)ssRNA]
Group 1 –
- Non-segmented genome
- Transcription of –ve RNA by RNA-dependent RNA polymerase to give monocistronic mRNA
- Ambisense organisation
Group 2 –
- Orthomyxoviruses (segmented genome)
- Monocistronic mRNA in nucleus
- Virus transcriptase in nucleocapsid
Example: Influenze virus

Group VI: reverse RNA
- (+)ssRNA with DNA intermediate
- Diploid
- Reverse transcription of viral RNA to dsDNA by viral RT
- Integration of dsDNA into host genome
- Viral RNA not used as mRNA
Example: HIV

Group VII: reverse DNA
- dsDNA with RNA intermediate
- not well understood
- overlapping reading frames
Example: hepatitis B virus

An animation about viral replication..
http://www.liquidjigsaw.com/animation/virus.htm

References:
http://en.wikipedia.org/wiki/Viral_replication
http://www.web-books.com/MoBio/Free/Ch1E2.htm

Varicella Zoster Virus

Varicella-zoster virus (VZV) causes chickenpox which usually mild, but may be severe in infants, adults, and people with impaired immune systems. Almost everyone gets chickenpox before the age of 20.

Chickenpox is highly contagious. The virus spreads from person to person by direct contact, or through the air. There is a high chance (around 90%) of contracting chickenpox if exposed to an infected family member.

The characteristics of chickenpox is having an itchy rash, which then forms blisters that dry and become scabs in 4-5 days. The rash may be the first sign of illness, sometimes coupled with fever and general malaise, which is usually more severe in adults. An infected person may have anywhere from only a few lesions to more than 500 lesions on his or her body during an attack. The averge is 300-400 lesions though.

Adults are more likely to have a more serious case of chickenpox with a higher rate of complications and death.

Chickenpox is contagious 1-2 days before the rash appears and until all blisters have formed scabs. Chickenpox develops within 10-21 days after contact with an infected person.
Varicella vaccine has been available since March 1995 and is approved for use in healthy children 12 months of age or older, and susceptible (i.e., no evidence of having had chickenpox in the past) adolescents and adults.

Varicella vaccine is highly effective in protecting against severe chickenpox. Cases of disease caused by the wild virus, which may occur in a small proportion of vaccinees, are typically very mild, with fewer than 50 skin lesions and no fever.

It is recommended that all children be routinely vaccinated at 12-18 months of age and that all susceptible children receive the vaccine before their 13th birthday. Many states in the USA require vaccination for entry into pre-school or public school beginning in 1999. The vaccine is also approved for susceptible adolescents and adults, especially those with close contact with persons at high risk for serious complications (e.g., health-care workers, family contacts of immunocompromised persons).

A history of chickenpox is considered adequate evidence of immunity.

A blood test is available to test immunity in persons who are uncertain of their history or who have not had chickenpox. Many of these persons will find that they are immune when tested and thus will not need to be vaccinated.

Effective medications (e.g., acyclovir) are available to treat chickenpox in healthy and immunocompromised persons (e.g, those with cancer, human immunodeficiency virus/AIDS; those receiving medications that depress the immune system).

Varicella zoster immune globulin (VZIG), an immune globulin made from plasma of healthy volunteer blood donors with high levels of antibody to VZV, is recommended after exposure for persons at high risk for complications (e.g., immunocompromised persons, pregnant women, premature infants)

Reference:

http://www.uhseast.com/120837.cfm

http://www.medhelp.org/NIHlib/GF-619.html

Retroviridae

Electron micrograph image of Feline Leukemia Virus, a virus in the Retroviridae family.

Higher order taxa
Viruses; Retro-transcribing viruses; Retroviridae

Genera
Orthoretrovirinae (subfamily)
Alpharetrovirus
Betaretrovirus
Deltaretrovirus
Epsilonretrovirus
Gammaretrovirus
Lentivirus
Spumaretrovirinae (subfamily)
Spumaretrovirus

Description and Significance
Retroviruses are viruses that are remarkable for their use of reverse transcription of viral RNA into DNA during replication. Members of this family include Human immunodeficiency virus (the virus that causes AIDS), feline leukemia, and several cancer-causing viruses. Retroviruses were discovered in 1908 by Vilhelm Ellermann and Oluf Bang. The first sixty years of study of retroviruses focused exclusively on animal infection and disease. In the 1960s and 1970s, study focused on the viral replication cycle and pathogenic effects at the cellular level. Current study of retroviruses focuses on the diverse pathogenic effects of these viruses at the cellular and molecular levels. Retroviruses were the first viruses to be modified for gene therapy, and continue to be used in the majority of gene therapy clinical trials.
(sources: Coffin et al., Hu and Pathak)

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. The encapsidated nucleic acid is mainly of genomic origin but virions may also contain nucleic acid of host origin, including host RNA and fragments of host DNA believed to be incidental inclusions. The complete genome of one monomer is 7000-11000 nucleotides long. The 5'-end of the genome has a methylated nucleotide cap with a cap sequence type 1 m7G5ppp5'GmpNp. The 3'-terminus of each monomer has a poly (A) tract and the terminus has a tRNA-like structure. (source: ICTVdB)

Virion Structure of a Retroviridae
The virions of a retroviridae consist of an envelope, a nucleocapsid and a nucleoid. The virus capsid is enveloped. The virions are spherical to pleomorphic and measure 80-100 nm in diameter. The surface projections are small or distinctive glycoprotein spikes that cover the surface evenly. The projections are densely dispersed and 8 nm long. The nucleoid is concentric or eccentric while the core is spherical. (source: ICTVdB)


Reproduction Cycle of a Retroviridae in a Host Cell
Retrovirus virions enter host cells through interaction between a virally-encoded envelope protein and a cellular receptor. Viral RNA is transcribed into a DNA copy by the enzyme reverse transcriptase which is present in the virion. The viral DNA copy is integrated into, and becomes a permanent part of, the host genome. This integrated DNA is referred to as a provirus. The host cell's transcriptional and translational machinery expresses the viral genes. The host RNA polymerase II transcribes the provirus to create new viral RNA, which is then transported out of the nucleus by other cellular processes. A fraction of these new RNAs are spliced to allow expression of some genes, while others are left as full-length RNAs. Viral proteins are synthesized by the host cell's translational machinery. Virions are assembled and bud from the host cell.

This reproduction cycle applies to all of the members of Retroviridae except for spumaviruses. Spumaviruses complete reverse transcription in the virus-producing cells rather than infected target cells, and the infectious virus contains a DNA genome. (source: Hu and Pathak)


Viral Ecology & Pathology
Retroviruses cause a wide variety of malignancies, immunodeficiencies, and neurological disorders affecting a wide variety of species. According to Coffin et al., "Some of these disorders have significant agricultural impact, crippling farm animals during their most productive years, whereas others have a devastating medical and economic impact on humans. Still others, particularly many of the retrovirus-induced malignancies of rodents, were found originally in laboratory settings and provide excellent model systems for probing the biological and molecular mechanisms of carcinogenesis." (source: Coffin et al.)

References:
Coffin et al. Retroviruses. Cold Spring Harbor Laboratory Press, 1997.
Hu, Wei-Shau and Vinay K. Pathak. "Design of Retroviral Vectors and Helper Cells for Gene Therapy." Pharmacological Reviews 52.4 (2000): 493-511.
ICTVdB - The Universal Virus Database, version 4. http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB

Herpsviridae

Herpesviridae is a heterogeneous family of morphologically similar viruses, all of which contain double-stranded DNA and infect humans and a wide variety of other vertebrates.

Infections produce type A inclusion bodies; in many instances, infection may remain latent for many years, even in the presence of specific circulating antibodies. Virions are enveloped, ether sensitive, and vary up to 200 nm in diameter; the nucleocapsids are 100 nm in diameter and of icosahedral symmetry, with 162 capsomeres.

Virus causes viral encephalitis. If passed from mother to baby during childbirth, brain damage may be caused to the baby.

The family is subdivided into three subfamilies:

1. Alphaherpesvirinae

- herpes simplex virus

- varicella-zoster virus,

2. Betaherpesvirinae

- cytomegalovirus

- human herpes type 6

- human herpes type 7

3.Gammaherpesvirinae

- epstein barr virus

- human herpes type 8

Herpesviridae: family of enveloped DNA viruses; occur in man, cold-blooded vertebrates, and invertebrates; some may induce neoplasia; transmission is usually by contact but it can occur by other routes.

Herpes simplex virus -

There's two type of HSV - HSV 1 and HSV 2. The virus can be primary or recurrent. On the infected patient may have cold sores around the mouth for one week or genital herpes for around one to three weeks, sometimes the eyes and gum may be affected too.

HSV 1 is spread by kissing or close proximity. According to the US stats, 100% of the adult population have carriers of HSV 1

HSV 2 is transmitted mainly via sexual contact. According to the US stats, up to 20% of the adult population are infected.

Electron Micrograph of Varicella Zoster

Reference: http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/00.031.htm

Smallpox

What is smallpox

An acute, highly infectious, often fatal disease caused by a poxvirus and characterised by high fever and aches with subsequent wide spread eruption of pimples that blisters, produce pus and forms pockmarks.

The history of smallpox

Smallpox is an acute contagious disease caused by the variola virus, a member of the orthopoxvirus family. It is one of the most devastating diesease known to mankind and throughout the centuries, repeated epidemics swept across the world, decimating populations and changing the course of history.

Smallpox, which had no effective treatment ever developed, killed as many as 30% of those infected. Between 65–80% of survivors were marked with deep pitted scars , most prominent on the face. Blindness was also another result from smallpox.

In the 18th century, smallpox killed every 10th child born in Sweden and France. During the same century, every 7th child born in Russia died from smallpox.

It was Edward Jenner's demonstration in 1798, to protect against smallpox by the inoculation of cowpox, that brought the first hope that the disease could be controlled.

The disease

Smallpox is caused by the variola virus that emerged in human populations thousands of years ago. Variola major is the severe and most common form of smallpox which has an overall fatality rate of about 30%. Variola minor is a less common presentation of smallpox, and a much less severe disease, with death rates of 1% or less.

Transmission

Smallpox can be spread through direct contact with infected bodily fluids or contaminated objects such as bedding or clothing.

Our short summary of the steps to smallpox:
- A layer of red splotches and constant high fever
- Tiny pimples form everywhere
- Pimples develop tiny blistery heads
- The heads grow larger and hurt badly
- The poxes enlarge into boils
- The crusting process begins ( the most fatal process in smallpox)
- The crust falls off
- The patient becomes immune to it after a period of time and may not get it again after that
- Someone else comes in contact with the crust and the cycle starts over again


Conclusion

Will smallpox return?
Maybe. Maybe not.

The USA finds reason to believe that terrorists may have gotten hold on some variola and mass produce it as a biological weapon. There could also be a possible way of making the smallpox virus immune to vaccines. This "Superpox" enhancement has been tested on mousepox and has been proven fatal even to immunized mice.

Some good news though:

• Its existance has been completely eradicted from nature.


• You dont have it.

Not much, but its enough to help people sleep at night. (:

The reality is that smallpox may not be here anymore now. But let us not forget what it did and possibly, what it can do.

In memory of those who died from smallpox.

references:
http://www.who.int/mediacentre/factsheets/smallpox/en/
www. youtube.com
http://www.smallpox.gov/smallpox/aboutdisease.html
www.learnnc.org