by Vincent RacanielloThursday, September 01, 2011 at 06:45 AM EDT

This article was written for extracredit by a student in my virology course.

Human papillomavirus (HPV) infection is the most common sexually transmitteddisease in the United States, and as of yet, there is no cure. however, thereis a vaccine to prevent infection by certain strains. Recent research mayencourage not just the young women of the world, but also the men, to rush totheir doctors for this vaccine. As the advertisements for Gardasil have taughtmany of us, certain strains of HPV are responsible for the majority of cervicalcancer cases. Now research is uncovering HPV as a major factor in several oralcancers as well. while men may have thought there was no need to get vaccinatedagainst HPV before, this new information may change things.

Human papillomavirus infects epithelial cells of skin and mucous membranes.Through skin abrasions caused by injury or sexual contact, the virus gainsaccess to the basal layer of the epithelial tissue, which is the lowest layerof the skin. HPV is a DNA virus that replicates in the epithelium at theprimary site of infection. Noncancerous strains, which cause papillomas (warts)or even no apparent symptoms, replicate in the basal epithelial cells. Theviral genome does not integrate into the host genome of the cell it infects,but instead replicates autonomously in a dividing cell. the productivity ofviral replication depends on the stage of cell differentiation. As the infectedcell moves to the upper level of the epithelium and begins to differentiate,viral replication becomes more productive. Replication producing highconcentrations of viral genomes and the assembly of new virus particles(virions) is restricted to the outer epithelial cells, which are fullydifferentiated and no longer divide.

In cancers caused by viral infection, the virus must transform the infectedcell, changing its growth properties and allowing for progression to cancer. Intransformed cells, the viral genome has integrated into the host genome. Whenthe viral DNA is integrated into the cellular genome, the viral mRNA that isthen transcribed can contain cellular DNA sequences and is subsequently morestable than sequences transcribed from a nonintegrated viral genome. Becausethe mRNA transcripts are more stable, viral proteins, specifically proteins E6and E7, are present in higher concentrations than in cells where the viralgenome is not integrated. These viral proteins E6 and E7 interfere with thecell cycle by restricting the activity of the cellular tumor suppressorproteins p53 and Rb. Specifically, E6 blocks apoptosis (programmed cell death)by inducing degradation of p53. In an uninfected cell, proteins Rb and p53sense DNA damage and prevent the cell cycle from progressing further. ProteinE7 binds Rb proteins, allowing the cell replication cycle to progress so thevirus can replicate. once a cell has been transformed, the cell replicationcycle goes unchecked and this can allow for the accumulation of mutations inthe cell’s DNA. this buildup of mutations and frequent cellular replication canlead to oncogenesis, the development of cancer. the specific strains that areassociated with these changes in epithelial tissue that can lead to cancer arestrains 16 and 18. These are the strains from which Gardasil protects anindividual, along with strains 6 and 11, which cause genital warts.

Researchers have studied oral cancers among men who are nonsmokers andnondrinkers, and discovered the presence of HPV in the biopsied tissues. Infact, some researchers are now claiming that the prevalence of HPV induced oralcancers is greater than cancers caused by both smoking and drinking combined.HPV is spread by direct skin-to-skin contact and sexual contact, and itsreplication is localized to the site of infection. Therefore, individuals whodo not engage in vaginal intercourse, but do engage in other forms of sexualcontact, such as oral sex, are still at risk for HPV infection. Virus is shedfrom the epithelial cells of the infected individual, even when the individualis asymptomatic. if an individual is orally infected with one of the high-riskstrains (either 16 or 18), the virus will replicate locally in the infectedtissue, and as described above, can cause cell transformation, leading tooncogenesis and tumor progression. because of these risks, the importance ofthis vaccine for both men and women is becoming blatantly apparent.

HockingJS, Stein A, Conway EL, Regan D, Grulich A, Law M, & Brotherton JM (2011).Head and neck cancer in Australia between 1982 and 2005 show increasingincidence of potentially HPV-associated oropharyngeal cancers. British journal of cancer, 104 (5), 886-91PMID: 21285981

This article originally appeared on virology blog.

Cystic fibrosis is a life-threatening affliction acquired by a abnormal gene and affecting about 30,000 accouchement in America. there is no cure for it so far, but there are lots of able abstracts and analytic studies activity on to accession a abiogenetic appraisal to cure cystic fibrosis.

Humans transmit the genetic code to the next generation through DNA, containing 23 pairs of chromosomes. the seventh chromosome contains the defective gene that causes cystic fibrosis. there are over ten million Americans who this defective gene without having the disease. When both parents are carriers there is a 25% chance that the child will have a recessive gene; that is, the child has two copies of the defective gene from both parents. this gene signals the epithelial cells to produce cystic fibrosis trans-membrane conductance regulator (cystic fibrosisTR). it is a bad protein found in the digestive system, skin and reproductive system of cystic fibrosis patients.

When the cystic fibrosisTR is not normal, the regulation of salt through the membranes becomes defective. this results in the secretions of the lining such as mucus, digestive juices and sweat, becoming thick and sticky.

The respiratory system secretes thin and slippery mucus to clear away the foreign bodies and microorganisms that invade the system. in cystic fibrosis patients this mucus, thick and sticky, not only fails to clean the system but also blocks the lungs and airways and creates a life-threatening problem with the respiratory system. As the microorganisms are not cleared there are serious infections, like bronchitis, pneumonia and influenza. So a cystic fibrosis patient has to take care of his respiratory system constantly, with bronchodilators, electrical clappers and electrical inflatable vest vibrators. Newer antibiotics control the infections to a good extent.

In the digestive system the ducts between the pancreas and intestine and between the liver and intestine are blocked. due to the shortage of enzymes and bile, the cystic fibrosis patient is unable to digest fats and proteins. He becomes malnourished, underweight and weak. Enzyme and vitamin supplements take care of the problem to an extent. in the reproductive system the duct between the testes and prostate get blocked, and so a majority of cystic fibrosis patients are sterile.

Cystic Fibrosis Symptoms

Cystic fibrosis is a very serious disorder that is fatal if not treated properly. a defective gene causes thin body secretions, such as lung mucus, digestive juices, sweat and reproductive secretions, to become thick and sticky. serious and life-threatening problems may arise due to this thickening. there is no permanent cure for cystic fibrosis yet, but symptomatic treatment is given.

When the lungs and airways are choked, the cystic fibrosis patient coughs and produces very thick sputum. He is short of breath and develops wheezing. Polyps may grow in the nasal passages. the frequency of sinus, chest infections, pneumonia and bronchitis increase.

As the digestive juices do not reach the intestine, due to blocked ducts from the pancreas and liver, the fats and protein are not digested. the stool is bulky, greasy and foul smelling. the cystic fibrosis patient may have excessive appetite but is undernourished and underweight, as the food is not digested properly for absorption. a trypsin test may indicate whether sufficient enzymes from the pancreas are available for digestion.

The sweat may taste salty. When we kiss a child with cystic fibrosis we can taste this excessive salt taste. To diagnose cystic fibrosis positively we measure this saltiness in sweat. Technicians coat an odorless chemical on a small area of the skin in the arm, and stimulate that area with electric current to produce copious sweat. this sweat should contain about 40 m mol/l in a normal person. above 60 m mol/l of salt in a sweat test will confirm the diagnosis of cystic fibrosis. With cystic fibrosis patients the duct that connects the testes and vas deferens may get blocked. Most cystic fibrosis patients are sterile.

Treatment is mainly to ease the symptoms and lead a normal life in spite of the malady. Bronchodilators and mechanical vibrators keep the lungs and airways clear. Enzyme and vitamin supplements keep the digestive system near normal. With correct lifestyle management Americans are living to their 30s and 40s with cystic fibrosis.

Cystic Fibrosis Treatments

Cystic fibrosis, which affects 30,000 American children and adults, is a multisystem disease caused by a defective gene. Presently only symptomatic management is possible, but there are very promising gene-therapy trials under way.

In the respiratory system the thin mucus lining becomes thick and sticky. in cystic fibrosis management, the primary treatment of the system is to thin or clear this mucus. Bronco dilators like albuterol are used to clear the clogged airways. Mucus thinning drugs delivered by aerosol, like pulmozyme, are helpful. the most effective way of clearing this mucus is by mechanically dislodging it. Clapping on the chest and back, with the head tilted on the edge of a table, is quite effective. there is an electrical clapper that does the job safely. there is an electrical inflatable vest that vibrates and dislodges the mucus. Infection is an ever-present risk with cystic fibrosis patients. Regular shots for pneumonia and influenza are very important. Bacterial infection is fought with newer antibiotics like TOBY, which delivers the medicine directly into airways with aerosols.

Because of the blocked ducts of the pancreas and liver, the enzymes and bile do not reach the intestine. though the patient eats normally or even in excess, the fats and proteins are not digested. So the cystic fibrosis patient needs to have the enzymes supplemented with oral pancreatic enzymes. there is also the need to take vitamins, especially the fat-soluble ones. if lung function is completely damaged, the only alternative would be lung transplantation. this would involve many factors, like the availability of a donor and the patient’s present health, prior to undergoing major surgery.

The Cystic Fibrosis Foundation has 115 centers all over America, and provides guidelines and advice. they support many studies to find gene therapy to cure cystic fibrosis. the target is to add normal genes to the cells of the airways to prevent further damage. Biotech laboratories produce healthy genes, which need to be delivered to the appropriate cells. these vectors, or delivery systems, are the key areas of research to combat cystic fibrosis. One method that is actively pursued is to modify the common cold virus to carry the healthy genes into the correct cells. on another track, the DNA molecules are compacted to their minimum size and delivered directly to the relevant cells without the need for a carrier such as a virus. this technology is called PLAS min.

As this gene therapy experiments are at an advanced stage, the cystic fibrosis sufferers can hope for a permanent cure in the near future.

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