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Viruses come in two basic types, those that have a genome of DNA and those that have a genome of RN. Viruses are composed of a genetic molecule surrounded by a protein coating called a capsid, and sometimes a membranous “envelope”. Within the capsid are distinct sub-units called capsomeres). The core is made of nucleic acid (either DNA or RNA, depending on the virus).
Some RNA viruses are retroviruses that use reverse transcription (i.e. HIV). Their RNA is used as a template for the host cell to make a DNA strand that functions as a template, making a complement DNA strand that forms a double helix. This DNA is incorporated into the host cell DNA as a provirus. The provirus is transcribed and used to make more virus RNA, which can then form new viruses that leave the cell ready to infect more cells.
Virus genetic material is more variable than that of living organisms. The virus genetic molecule has from 4 to a few hundred genes and is either a single linear nucleic acid or a circular nucleic acid molecule. The genetic molecule can be:
A membranous coating or viral envelope may enclose a number of individual virus particles. The human flu virus is an enveloped virus that has 8 RNA molecules, each with its own capsid.
Adenoviruses are double-stranded DNA viruses.
Adenovirus usually causes a localized infection; the incubation period is 5 to 8 days. Adenovirus is responsible for five percent of acute respiratory childhood illness and ten percent of infantile gasteroenteritis.
Meningoencephalitis is a complication of respiratory adenovirus infection. Deaths may occur from adenovirus especially from infection by human adenovirus type seven. Diagnosis occurs through enzyme immunoassay, immuno-fluorescence techniques and virus isolation in cell cultures.
Antivirals have generally been ineffective against adenovirus infection. Intravenous ribavirin is a potential treatment. Adenovirus infection results in long-lasting immunity against the specific serotype. Maternal antibody is protective.
The following strategies should be implemented to prevent adenovirus diseases:
The vaccine against adenovirus is live. Vaccines are administered to the military, but not available for general use because of concern about the live vaccine’s oncogenic potential and the level of attenuation.
RNA viruses are any group of viruses whose nucleic acid core is composed of RNA; this includes the picornaviruses, retroviruses, and paramyxoviruses. An RNA virus is a virus that either uses RNA as its genetic material or whose genetic material passes through an RNA intermediate during replication. For example, Hepatitis B virus is classified as an RNA virus, even though its genome is double-stranded DNA, because the genome is transcribed into RNA during replication.
All RNA viruses have very high mutation rates because they lack DNA polymerases that can find and edit out mistakes. Each surviving virus can reproduce itself hundreds or thousands of times and mutates easily. It has been estimated that a typical RNA virus may experience alterations of between .03 and 2 percent of its entire genome each year - evolving faster than any other living organism.
There are two kinds of RNA viruses, those that have a “sense” strand of RNA (coded information about how to build proteins) as their genetic material, and those that have an “antisense” strand (the paired opposite of the coded information). Hepatitis C is of the “sense” type.
Ribozyme is an RNA molecule that catalyzes a chemical reaction. Before the discovery of ribozyme, proteins were thought to be the only known biological catalysts. Thomas Cech who was studying the RNA splicing discovered the first ribozyme in 1980.
Coronaviruses get their name from their striking halo corona (crown) of spikes from the Coronaviridae family on the electron microscope. The corona or halo is due to an array of surface projections on the viral envelope, one of which is the E2 glycoprotein, the viral attachment protein and target of neutralizing antibodies.
Coronaviruses primarily infect the upper respiratory and gastrointestinal tract. The most published human coronavirus, SARS-CoV, has a unique pathogenesis because it causes both upper and lower respiratory tract infections and can also cause gastroenteritis.
Coronaviruses are believed to cause a significant percentage of all common colds. In fact, coronaviruses are second only to rhinoviruses as a cause of the common cold. The significance of coronaviruses as causative agents is hard to assess because, unlike rhinoviruses (another common cold virus), coronaviruses are difficult to grow in the laboratory. Diseases caused by coronaviruses include common colds and pneumonia.
Although RNA usually mutates rapidly, recent research found that the SARS virus and related RNA viruses contain a gene that mutates very slowly. The gene in question has a complex three-dimensional structure that is hypothesized to provide a chemical function necessary for viral propagation. Four to five of the total isolated strains of coronaviruses infect humans. The discovery of SARS-CoV added another human coronavirus to the list.
Severe Acute Respiratory Syndrome, SARS, is a mystery virus that swept across parts of Asia and the Far East, and then moved worldwide. It is thought that the virus originated in the Guangdong province in southern China, with neighboring Hong Kong being one of the main centers of the outbreak. It is believed that a combination of two viruses, coronavirus and Paramyxovirus, might cause the more deadly variation that created so many sudden illnesses.
The main symptoms of SARS are high fever, combined with dry cough, shortness of breath, headache, muscle stiffness, loss of appetite, confusion, rash, and diarrhea. SARS transmission is by respiratory droplets spread through close contact with an infected person. The clinical diagnosis is based on serology studies. The incubation period is estimated between two and seven days.
The spread of the disease prompted Singapore, Hong Kong and parts of Canada to close certain public places and invoke a quarantine law that affected people thought to have had close contact with others showing signs of infection.
Caliciviruses are a group of viruses belonging to the family Caliciviridae. All of the caliciviruses are single-stranded RNA, non-enveloped viruses.
The best known of these viruses is Norovirus, once called Norwalk-like virus, that causes gastroenteritis.
The virus is spread primarily from one infected person to another by the fecal-oral route. A common method of transmission is for infected kitchen workers to contaminate a salad or sandwich because they have the virus on their hands while preparing it. Norovirus infection became well known because of outbreaks on cruise ships.
Orthomyxoviruses are single-stranded, negative-sensed RNA viruses known as the influenza virus, and is the most frequent cause of acute respiratory illness. It can affect all age groups and can reoccur in individuals, no matter how many times the person has been previously infected.
The influenza virus replicates in the columnar epithelial cells of the respiratory tract, which is the virus is integrated into the respiratory secretions of the infected person and are therefore spread to others
The virus is spread person to person via small particle aerosols (less than 10ìm) that can get into respiratory tract. It can also survive for a short time on surfaces and can be spread by this route if the virus is introduced into the nasal mucosa before it loses infectivity. The incubation period is short, about 18 to 72 hours.
Virus concentration in nasal and tracheal secretions remains high for 24 to 48 hours after symptoms start
Influenza virus infects the epithelial cells of the respiratory tract. Cell death at later times may also result from the actions of cytotoxic T-cells. As a result, the efficiency of ciliary clearance is reduced, leading to impaired function of the mucus elevator; thus there is reduced clearance of infectious agents from the respiratory tract. Gaps in the protective epithelium provide pathogens with access to other cells.
Isolated in the 1930’s, picornaviruses are among the most diverse (more than 200 serotypes) and “oldest” known viruses. The name picornavirus means small RNA virus. Picornaviruses are non-enveloped, positive-stranded RNA viruses with a different shape.
Based on properties such as acid sensitivity, etc. there are nine genera within the picomavinidae. Five of these infect humans. They are:
Within the enterovirus genera, there is polio, echo, coxsakie A and B, and other viruses that are picoviruses.
Coxsackie virus causes acute myositis (muscular inflammation) with inflammation and necrosis and can cause degenerative “plaques” in brain, muscle and pancreas, and myocarditis.
Echovirus causes Meningitis.
Hepatitis A virus causes infectious hepatitis.
Poliovirus causes poliomyelitis.
Rhinovirus causes common cold.
Paramyxovirus (Paramyxovirida family): These are viruses that are single stranded RNA. They are responsible for acute respiratory diseases.
Infection is via an aerosol route and the virus is very contagious. It replicates initially in the upper/lower respiratory tract, followed by replication in lymphoid tissues leading. The disease develops 1 - 2 weeks after infection. The following diseases are caused by paramyxovirus
Prior to the advent of the current measles vaccine, there were about 500,000 cases of measles in the United States per year — almost everyone contracted measles during their lifetimes. But since 1963 and vaccination, the number has fallen with a low of only 86 cases in 2001, all of which seem to be imported.
In the less developed world, measles still takes its toll with an estimated 30 million illnesses and 770,000 measles-caused deaths in 2000 of which 58% were in Africa. Measles is still a major killer in underdeveloped countries and in areas with severe vitamin A deficiency. It was found that vitamin A treatment of children with measles has resulted in reduction in morbidity and mortality. Pneumonia accounts for 60% of deaths from measles.
Although recovery is usually rapid, the peak of infectiousness is before the onset of obvious symptoms (Koplik’s spots, rash). If a patient has an impaired cell-mediated immune response, there is continued growth of the virus in the lungs leading to giant cell pneumonia (such patients may not have a rash). Although rare, it can be fatal. Since virus grows in epithelia of the nasopharynx, middle ear and lung, all of these sites may then be susceptible to secondary bacterial infection. Otitis media and bacterial pneumonia are quite common.
The nourishment of the patient and access to medical care affect the outcome of the disease. One in 1,000 cases may get encephalitis a few days after the rash disappears. Most patients (90%) survive encephalitis, but there may be complications such as deafness, seizures and mental disorders. Very rarely (7 in 1,000,000 cases) the patient may get subacute sclerosing panencephalitis (SSPE). This develops 1 to 10 years after the initial infection. It is a progressive, usually fatal disease and those who survive are severely impaired mentally and physically.
Nipah virus is a newly recognized zoonotic virus. In 1998-1999 in Nipah, Malaysia, and soon after in Singapore, people began developing brain inflammation (encephalitis), and in many cases this quickly progressed to coma and death. In all, 265 people were infected and 105 of them died (40% mortality rate). Ninety-three percent of cases had occupational exposure to pigs.
In February 2004, 47 people in Bangladesh became infected with Nipah virus in two outbreaks, 35 of them died (74% mortality rate). Although person-to-person transmission of Nipah virus has not been reported, the outbreaks in Bangladesh are cause for concern. No contact with pigs or any other infected domestic animals was found among the victims. Therefore, it can’t be ruled out that infected people passed Nipah virus to other people. This would be cause for alarm, since worldwide travel would give the virus the ability to reach many more people outside of the geographic area of an outbreak.
Some antivirals had positive effects upon the virus, but only minimized symptomology slightly. Scientists did not know of the existence of Nipah virus until people started to become ill and die.
Encroaching on the habitat of animals by deforestation or by building homes in wildlife areas brings people into contact with animals in new ways. This may permit animal viruses to cross over into humans.
The incubation period is between 4 and 18 days. In many cases the infection is mild or sub-clinical. In symptomatic cases, the onset is usually with “influenza-like” symptoms, with high fever and myalgia. The disease may progress to encephalitis with drowsiness, disorientation, convulsions and coma. Fifty percent of clinically apparent cases die.
Retrovirus is a class of enveloped RNA viruses that have their genetic material in the form of RNA, but use the reverse transcriptase enzyme to translate their RNA into DNA in the host cell. Reverse transcriptase allows many copies of the virus to be made in the host cells. The virus that causes AIDS, the human immunodeficiency virus (HIV) is a type of retrovirus.
The first substantially pure preparations of retroviruses became available in the 1960s, for the avian sarcoma/leukosis viruses and the murine leukemia viruses (the most widely studied retroviruses) until the human immunodeficiency virus (HIV). Retroviruses are broadly divided into two categories—simple and complex—distinguishable by the organization of their genomes.
The latest statistics on the world epidemic of AIDS & HIV were published by UNAIDS/WHO in November 2005. In 2004, there were around 5 million adults and children infected with HIV. At the end of that year, 40.3 million people were living with AIDS. Today, there are:
HIV, the virus that causes AIDS (acquired immunodeficiency syndrome), is a retrovirus with two RNA molecules that may not be identical. A retrovirus uses reverse transcriptase which makes its genetic information flow in reverse (RNA to DNA) instead of (DNA to RNA).
The global illness of HIV/AIDS is an enormous health crisis of our time. More than 6,000 people become infected with HIV daily. Human Immunodeficiency Virus (HIV) presents a complex knot for scientists to unravel. After initial contact and attachment to a cell of the immune system (e.g. lymphocytes, monocytes), there is a cascade of intracellular events. The end product of these events is the production of massive numbers of new viral particles, death of the infected cells, and ultimate devastation of the immune system.
“Almost 5 million people were infected by HIV globally in 2005; the highest jump since the first reported case in 1981, taking the number living with the virus to a record 40.3 million, according to the United Nations.” (Reuters 8-05 New Delhi). According to the CDC, there are as many as 950,000 Americans that may be infected with HIV, one-quarter of who are unaware of their infection,
Acquired immunodeficiency syndrome (AIDS) is a fatal disease caused by a rapidly mutating retrovirus that attacks the immune system and leaves the victim vulnerable to infections, malignancies, and neurological disorders. The term AIDS applies to the most advanced stages of HIV infection. The CDC developed official criteria for the definition of AIDS and is responsible for tracking the spread of AIDS in the United States.
AIDS was first reported in the United States in 1981 and has since become a major worldwide epidemic. By killing or damaging cells of the body’s immune system, HIV progressively destroys the body’s ability to fight infections and certain cancers. People diagnosed with AIDS may get life-threatening diseases (opportunistic infections) that are caused by microbes that usually do not make healthy people sick. There is no cure for AIDS as of this writing.
The CDC’s definition of AIDS includes all HIV-infected people who have fewer than 200 CD4+ T cells per cubic millimeter of blood. (Healthy adults usually have CD4+ T-cell counts of 1,000 or more.)
In addition, the definition includes 26 clinical conditions that affect people with advanced HIV disease. In people with AIDS, these infections are often severe and sometimes fatal because the immune system is so ravaged by HIV that the body cannot fight off certain bacteria, viruses, fungi, parasites, and other microbes.
Symptoms of Opportunistic Infections Common in People with AIDS Include:
Two different types of antibody tests are utilized to diagnose HIV, they are: ELISA and Western Blot. HIV antibodies generally do not reach noticeable levels in the blood for 1 to 3 months following infection. It may take the antibodies as long as 6 months to be produced in quantities large enough to show up in standard blood tests.
Thus far, four human retroviruses (HTLV 1 and 2 in conjunction with HIV 1 and 2) have been found to attack helper T cells. In 1999 an international team of genetic scientists reported that HIV-1 was traced to a closely related strain of virus, called simian immunodeficiency virus (SIV), infecting a subspecies of chimpanzee in West central Africa. Because chimpanzees are hunted for meat in this region, it was believed the virus might have passed from the blood of chimpanzees into humans through superficial wounds, probably in the early 1930s.
In a process still imperfectly understood, HIV infects the CD4 cells (T4 or T-helper cells). Although billions of lymphocytes are created daily to fight copius copies of the virus, the immune system is eventually overwhelmed, and the body is left vulnerable to opportunistic infections and cancers.
Some people develop flu like symptoms shortly after infection, but many have no symptoms. It may be a few months or many years before serious symptoms develop in adults; symptoms usually develop within the first two years of life in infants infected in the womb or at birth. Before serious symptoms occur, an infected person may experience fever, weight loss, diarrhea, fatigue, skin rashes, and shingles. Some people develop flu-like symptoms shortly after infection, but many have no symptoms.
These infections conspire to cause a wide range of symptoms, i.e., coughing, diarrhea, fever, night sweats, and headaches, and may lead to extreme weight loss, blindness, hallucinations, and dementia before death occurs.
Viral load tests are reported as the number of HIV copies in a milliliter of blood. If the viral load measurement is high, it indicates that HIV is reproducing and that the disease will likely progress faster than if the viral load is low. A high viral load can be anywhere from 5,000 to 10,000 copies and can range as high as one million or more.
A low viral load is usually between 200 to 500 copies, depending on the type of test used. This result indicates that HIV is not actively reproducing and that the risk of disease progression is low. A viral load result that reads ‘undetectable’ does not mean that a person is cured. It may mean that the level of HIV virus in the blood is below the threshold needed for detection by this test. Some tests that are ultra-sensitive can measure as few as 20 to 40 copies in a milliliter of blood.
Changes in the viral load are also a very important measurement. A rising count indicates an infection that is getting worse, while a falling count indicates improvement and suppression of the HIV infection. A non-infected person should have no circulating HIV virus in his or her blood and, therefore, a negative or undetectable viral load.
Transmission of the HIV virus requires a direct exchange of body fluids, such as blood or blood products, breast milk, semen, or vaginal secretions. It is most commonly transmitted as a result of sexual activity or the sharing of needles among drug users.
At the end of 2002 it was estimated that 42 million people were infected with HIV worldwide, the great majority in Third World countries; some 25 million had died from AIDS. The disease in sub-Saharan Africa, which has been especially hard hit, has been transmitted primarily heterosexually but has been exacerbated by civil wars, refugee problems and less restrictive local mores in regards to sex. Some 29 million people were infected with HIV in this region, where, in many countries, the prevalence of AIDS has lowered the life expectancy. The epidemic also has manifested itself in Asia and Latin America.
Some 30 experimental AIDS vaccines have been developed and tested, but none has yet proved clearly effective. The development of a successful vaccine against AIDS has been slowed because HIV mutates rapidly, causing it to become unrecognizable to the immune system and because, unlike most viruses, HIV attacks and destroys essential components of the very immune system a vaccine is designed to stimulate.
Although there is no cure, there have been reverse transcriptase inhibitors that delay the symptoms. Protease inhibitors interrupt the virus from making copies of itself at a later step in its life cycle. They include:
Another class of drugs, known at fusion inhibitors, treats HIV infection. Fuzeon (enfuvirtide or T-20) works by interfering with HIV-1’s ability to enter into cells by blocking the merging of the virus with the cell membranes. This inhibition blocks HIV’s ability to enter and infect the human immune cells. Fuzeon is designed for use in combination with other anti-HIV treatment.
Because HIV can become resistant to any of these drugs, health care providers must use a combination treatment to effectively suppress the virus. When multiple drugs (three or more) are used in combination, it is referred to as highly active antiretroviral therapy, or HAART, and can be used by people who are newly infected with HIV as well as people with AIDS.
Researchers have credited HAART as being a major factor in significantly reducing the number of deaths from AIDS in this country. While HAART is not a cure for AIDS, it has greatly improved the health of many people with AIDS and it reduces the amount of virus circulating in the blood to nearly undetectable levels. Researchers, however, have shown that HIV remains present in hiding places, such as the lymph nodes, brain, testes, and retina of the eye, even in people who have been treated.
HIV is a reverse transcriptase retrovirus.
Only activated T4 cells can replicate virus
Most infected T4 cells are rapidly lysed but are replaced
Some T4 cells revert to resting state as memory cells which are long-lived
Memory T4 cells cannot replicate the virus unless they become activated
HIV infection is not manifested as disease for years
During apparent clinical latency, virus is being replicated and cleared
Massive loss of CD4+ cells
At early stages of infection only 1 in 10,000 cells is infected
Late 1 in 40(Inexorable decline of CD4+ T4 cells)
CD4+ cells are the targets of the virus
Cells that proliferate to respond to the virus are killed by it
Dendritic cells present antigen and virus to CD4 cells
Epitope variation allows more and more HIV to escape from immune response just as response wanes
Apoptosis of CD4+ cells
CD8+ cells destroy more CD4+ cells
CD4 cell loss means virus and infected
cells no longer controlled
As CD4+ cells fall below 200 per cu mm
virus titer rises rapidly and remaining immune response collapses
CD8+ cell number collapses
Opportunistic infection enter
Death in ~2 years without intervention
Viral load predicts survival time
So far it seems that >50% of HIV-infected persons have progressed to AIDS HIV genome 9749 nucleotides: Therefore EVERY new virus has at least one mutation!
Lentiviruses are a subgroup of retroviruses, characterized as slow-growing viruses and normally found in non-human primates. One of the lentiviruses found in monkeys is the simian immunodeficiency virus (SIV). Research on the human immune deficiency virus has found a close resemblance to the simian immunodeficiency virus.
HIV belongs to the lentivirus family of retroviruses. Although the first case (HIV) was reported in the USA in 1981, research into the origin of the disease has since shown that the virus was present in man long before it was documented.
Studies on chimpanzees in the 1980s to determine if a link existed between the viruses showed that when deliberately injected with HIV, the monkeys did not develop HIV/AIDS. In 1999, a clear link was established between SIV and HIV based on genetic testing performed on frozen blood and tissue samples taken from a sub-species of chimpanzee (found in central-west Africa).
Rotavirus is the most common cause of severe diarrhea among children, resulting in the hospitalization of approximately 55,000 children each year in the United States and the death of over 600,000 children annually worldwide. The primary mode of transmission is fecal-oral, although some transmission occurs through ingestion of contaminated water/food and contact with contaminated surfaces.
Rotavirus is easily spread by hand-to-mouth contact with stool from an infected person. The virus can be passed from one person to another by touching a hand contaminated by the virus. Merely touching a surface or object that has been contaminated by an infected person can also transmit the virus.
Viruses come in two basic types: those that have a genome of DNA and those that have a genome of RNA. Adenoviruses are double-stranded DNA viruses. Adenovirus is responsible for five percent of acute respiratory childhood illness and ten percent of infantile gastroenteritis.
RNA viruses are any group of viruses whose nucleic acid core is composed of RNA; this includes the picornaviruses, retroviruses, and paramyxoviruses. All RNA viruses have very high mutation rates because they lack DNA polymerases that can find and edit out mistakes.
Orthomyxoviruses are single-stranded, negative-sensed RNA viruses known as the influenza virus, the most frequent cause of acute respiratory illness. This is one of the reasons people fear the mutation of the avian flu.
Coronaviruses primarily infect the upper respiratory and gastrointestinal tract. The most published human coronavirus, SARS-CoV, has a unique pathogenesis because it causes both upper and lower respiratory tract infections and can also cause gastroenteritis.
Picornaviruses are among the most diverse (more than 200 serotypes) and “oldest” known viruses and were discovered in the 1930’s. There are nine genera within the picomavinidae. Five of these infect humans.
Paramyxovirus is a group of RNA viruses predominantly responsible for acute respiratory diseases spread by an airborne transmission. The paramyxoviruses include measles, mumps, RSV (respiratory syncytial virus) parainfluenza. Many of the paramyxoviruses cause disease in animals such as canine distemper.
Retroviruses are broadly divided into two categories—simple and complex—distinguishable by the organization of their genomes. They are a class of enveloped viruses that have their genetic material in the form of RNA but use the reverse transcriptase enzyme to translate their RNA into DNA in the host cell. HIV is a type of retrovirus.
There are currently 4 known retroviruses. Lentiviruses are a subgroup of retroviruses, characterized as slow-growing viruses and normally found in non-human primates. One of the lentiviruses found in monkeys is the simian immunodeficiency virus (SIV). HIV belongs to the lentivirus family of retroviruses.
Rotavirus is the most common cause of severe diarrhea among children, resulting in the hospitalization of approximately 55,000 children each year in the United States and the death of over 600,000 children annually worldwide. Rotavirus is easily spread by hand-to-mouth contact with stool from an infected person.