Virus Classification

Group: Group V ((-)ssRNA) Family: Orthomyxoviridae Genera

Influenzavirus A Influenzavirus B Influenzavirus C Isavirus Thogotovirus

Orthomyxoviruses

• Enveloped, segmented ssRNA
• 2 types of enveloped glycoprotein spikes
– Hemagglutinin (HA) – binds to host cells
– Neuraminidase (NA) – hydrolyzes mucus & assists viral budding & release
• Genome constantly changes
– Antigenic drift -minor change caused by mutations
– Antigenic shift -major alteration occurring when segments recombine

Q: What are hemagglutinin and neuraminidase?
a. Exotoxins produced by the influenza virus
b. Glycoprotein receptors on influenza's target cells
c. Glycoproteins on influenza virus that contribute to virulence
A: Glycoproteins on influenza virus that contribute to virulence




Influenza type A
• Acute, highly contagious respiratory illness
• Seasonal, pandemics • Among top 10 causes of death in US
• Respiratory transmission
• Binds to ciliated cells of respiratory mucosa
• Causes rapid shedding of cells, stripping the respiratory epithelium, severe inflammation fever, headache, myalgia, pharyngeal pain, shortness of breath, coughing
• Treatment: amantadine, rimantadine, zanamivir & oseltamivir annual trivalent vaccine

• Tested by inserting a swab into the nasopharyngeal area and testing the mucus on the swab. It can also be detected using what is called a nasal wash (shown below) where approximately 1 cc of saline is placed into a syringe with a hose attached to the syringe. (where the needle would be) The tubing is then placed up the nostril and the saline is shot up into the nostril. The saline is then sucked back into the syringe, collecting mucus in the process. Afterwards the solution is sent to the lab for testing. These tests can be performed to detect Influenza A and B. In the state of Utah if a Influenza B is detected it is sent to the State lab for verification.

Pandemics
Flu spreads around the world in seasonal epidemics, resulting in the deaths of hundreds of thousands annually — millions in pandemic years. Three influenza pandemics occurred in the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new strain of the virus in humans. Often, these new strains result from the spread of an existing flu virus to humans from other animal species. An avian strain named H5N1 had until recently posed the greatest risk for a new influenza pandemic since it first killed humans in Asia in the 1990s. Although H5N1 virus has not mutated to a form that spreads easily between people, in April 2009 a novel H1N1 flu strain that combined genes from human, pig, and bird flu, initially dubbed the "swine flu," emerged in Mexico, the United States, and several other nations. By late April, the H1N1 swine flu was suspected of having killed over 150 in Mexico, and prompted concern that a new pandemic is imminent.
The 2009 flu outbreak in humans that is widely known as "swine flu" apparently is not due to a swine influenza virus. It is due to a new strain of influenza A virus subtype H1N1 that derives from one strain of human influenza virus, one strain of avian influenza virus, and two separate strains of swine influenza virus. The origins of this new strain are unknown, and the World Organization for Animal Health (OIE) reports that this strain has not been isolated in swine. It passes with apparent ease from human to human, an ability attributed to an as-yet unidentified mutation. The strain in most cases causes only mild symptoms and the infected person makes a full recovery without requiring medical attention and without the use of antiviral medicines.





Reassortment: most important for pandemic influenza viruses
It is the mixing of the genetic material of two similar viruses that are infecting the same cell. In particular, reassortment occurs among influenza viruses, whose genomes consist of eight distinct segments of RNA. These segments act like mini-chromosomes, and each time a flu virus is assembled, it requires one copy of each segment.
If a single host (a human, a chicken, or other animal) is infected by two different strains of the influenza virus, then it is possible that new assembled viral particles will be created from segments whose origin is mixed, some coming from one strain and some coming from another. The new reassortant strain will share properties of both of its parental lineages.
Reassortment is responsible for some of the major genetic shifts in the history of the influenza virus. The 1957 and 1968 pandemic flu strains were caused by reassortment between an avian virus and a human virus, whereas the H1N1 virus responsible for the 2009 swine flu outbreak had an unusual mix of swine, avian and human influenza genetic sequences.







1918-1919 Flu Pandemic
-One out of every five people on earth were infected, with a 2.5% mortality rate (typical influenza is less than 0.1% fatal).
-The disease progressed very quickly and was sometimes fatal within hours.
-Some believe it to have been the avian flu
-It was most deadly for people between the ages of 20-40 years old which is an unusual pattern for influenza.
-675,000 Americans died which was 10 times more than in WWI.

This link has the full history of the1918 flu pandemic, incredible!

http://health.discovery.com/centers/coldsflu/germs/influenza.html

Q: What type of vaccine is the current flu vaccine?
a. Recombinant
b. Killed, whole virus
c. Toxoid
A: Killed, whole virus

Avian Influenza A (H5N1) Bird Flu
Influenza A (H5N1) is an influenza A virus subtype that occurs mainly in birds. It is highly contagious among birds and can also be deadly to them.
H5N1 virus usually does not infect humans but have on rare occasions. Most of these cases have been from direct or close contact with infected poultry. There is no immune protection against the human population. Infected birds shed influenza virus in their saliva, nasal secretions, and feces. Susceptible birds become infected when they have contact with contaminated secretions or excretions or with surfaces that are contaminated with secretions or excretions from infected birds. Domesticated birds may become infected with avian influenza virus through direct contact with infected waterfowl or other infected poultry, or through contact with surfaces (such as dirt or cages) or materials (such as water or feed) that have been contaminated with the virus.
Infection with avian influenza viruses in domestic poultry causes two main forms of disease that are distinguished by low and high extremes of virulence. The “low pathogenic” form may go undetected and usually causes only mild symptoms (such as ruffled feathers and a drop in egg production). However, the highly pathogenic form spreads more rapidly through flocks of poultry. This form may cause disease that affects multiple internal organs and has a mortality rate that can reach 90-100% often within 48 hours.

Mumps

• Epidemic Parotitis
• Self-limited, associated with painful swelling of
parotid salivary glands
• Humans are the only reservoir
• 40% of infections are sub-clinical
• 300 cases in US/year
• Incubation 2-3 weeks fever, muscle pain & malaise,
classic swelling of both cheeks
• In 20-30% of infected males, epididymis & testes become
infected; sterilization is rare
• Live attenuated vaccine MMR


Measles
• Caused by Morbillivirus
• Also known as red measles & rubeola
• Different from German measles
• Very contagious
• Transmitted by respiratory aerosols
• Humans are the only reservoir. Less than 100 cases/yr in US
• Virus invades respiratory tract
• Sore throat, dry cough, headache, conjunctivitis, lymphadenitis,
and fever, skin rash and oral lesions called Koplik's spots



RSV
• Also called Pneumovirus
• Infects upper respiratory tract & produces giant multi-nucleate cells
• Most prevalent cause of respiratory infection in children 6 months
or younger; most susceptible to serious disease
• Epithelia of nose & eye portal of entry
• Replicates in nasopharynx
• Rhinitis, wheezing, otitis, croup
• Treatment: Synagis, a monoclonal antibody that blocks attachment,
and ribavirin 5 out of a 1000 babies will be infected.




Rabies
-Rhabdovirus family; genus Lyssavirus
-Bullet-shaped, enveloped virions
-Slow, progressive zoonotic disease
-Virus enters through bite, grows at trauma site for a
week, enters nerve endings & advances toward the
ganglia, spinal cord & brain.
-Furious form of rabies – agitation, disorientation,
seizures, twitching, hydrophobia
-Dumb form of rabies – paralyzed, stuporous
-Often diagnosed at autopsy – intracellular inclusions
(Negri bodies) in nervous tissue
-Raccoons are the most common carriers U.S., but
bats are most likely to infect humans.
-Skunks and foxes also a carrier
-Few cases reported in wolves, coyotes, bobcats, and ferrets
-Smaller rodents (squirrels, mice, rabbits)-not a typical carrier
-10% of cases become fatal and 90% of infections are from dogs
-Vaccine can stop infection after infection has started
-Often autopsy diagnosed-intracellular inclusions & nervous tissue
-Treatment is passive and active post-exposure immunization
-Louis Pastuer made first vaccine for


Coronavirus (SARS)
A large RNA virus with distinctively spaced spikes on their envelopes. They are very common in domesticated animals. Three types or Coronaviruses have been characterized: HCV causes a cold, an enteric virus, and SARS which is transmitted air born and is 10% fatal.

• Guillian Barre Syndrome
• a neroligical complication that can arise in approxiamtely one in 10,000 vaccine recipients.
• syndrome appears to autoimmunity induced by viral proteins and marked by varying degress of demyelenation of the peripheral nervous system, leading to weakness and sesnsory loss.
• most patients recover function, but the disease can also be debilitating and fatal

Rubella (German Measles)
• Caused by Rubivirus,a Togavirus
• ssRNA with a loose envelop
• Teratogenic effects- cataracts, other congenital defects
• Transmitted through contact with respiratory secretions
• Postnatal rubella – malaise, fever, sore throat, lymphadenopathy, rash, generally mild
• Congenital rubella – infection during 1st trimester most likely to induce miscarriage or multiple defects such as cardiac abnormalities, ocular lesions, deafness, mental & physical retardation
• Attenuated viral vaccine MMR


Arboviruses
Since vertebrates are hosts to more than 400 viruses tranmitted primarily by arthropods, they are often lumped together in a loose grouping called the arboviruses (arthropod-borne viruses).
Epidemiology
Because arthropod vectors (mosquitoes, ticks, flies & gnats) are found worldwide, so too are the arboviruses they carry. Prevalence tends to be in the tropics and subtropics, but they are also prevalent in wilderness areas. All aspects of the arbovirus life cycle are closely tied to the ecology of the vectors. Factors that weigh most heavily are the arthropod's life span, the availability of food and breeding sites, and climatic influences such as temperature and humidity. Most arthropod vectors become infected by feeding on the blood of hosts. Infections show a peak incidence from late spring through early fall, when the arthropod is actively feeding and reproducing. Warm-blooded vertebrates also maintain the virus during the cold and dry seasons. Humans can serve as dead-end accidental hosts or they can be a maintenance reservoir.
Arboviral diseases have a great impact on humans. Although exact statistics are unavailable, there is a consensus that millions of people acquire infections each year and thousands of them die. The uncertain nature of vector and viral cycles frequently results in sudden, unexpected epidemics, sometimes with previously unreported viruses. Travelers and military personnel entering endemic areas are at special risk because, unlike the natives of that reigion, they have no immunity to the viruses.





Retroviruses
• Enveloped, ssRNA viruses
• Encode reverse transcriptase enzyme which makes a DNA copy of their RNA genome
• Human Immunodeficiency Virus (HIV) the cause of Acquired Immunodeficiency Syndrome (AIDS)
• HIV-1 & HIV-2
• T-cell lymphotropic viruses I & II – leukemia

CD4+ T cells
White blood cells that orchestrate the immune response, signaling other cells in the immune system to preform their special functions. They are also known as T helper cells. These cells are killed or disabled during HIV infection.
A healthy person has between 800 ans 1200 CD4+T cells per cubic millimeter of blood. During untreated HIV infection, the number of these cells in a person's blood progressively declines. If the CD4+T cell count falls below 200/mm3, a person will become vulnerable to the opportunistic infections and the cancers that typify AIDS, the end stage of HIV disease.

HIV


• Attacks the T helper cells & macrophages
• First signs of AIDS are opportunistic infections such as Pneumocystis Carinii Pneumonia (PCP) and cancers such as aposi sarcoma
• HIV attaches to CD4 & a co-receptor, XCR4
• HIV fuses with cell membrane; reverse transcriptase makes a DNA copy of RNA
• Viral DNA is integrated into host chromosome (provirus)
• Can produce a lytic infection or remain latent

• Tested with a simple blood test. It can be tested with the regular blood test that may take several days to a week. It can also be tested with a rapid H.I.V. test, which is more beneficial for persons who may have recently been exposed to blood. The rapid test is more beneficial, because if H.I.V. is detected, anti-viral medications can be administered after the rapid test is finished (only four hours).

Progression of HIV disease
• Initial infection – mononucleosis-like symptoms that soon disappear
• Asymptomatic phase 2-15 years
• Antibodies are detectable 8-16 weeks after infection
• HIV destroys the immune system
• When T4 cell levels fall below 200/μL symptoms appear including fever, swollen lymph nodes, diarrhea, weight loss, neurological symptoms, opportunistic infections & cancers
• Treatments, inhibit viral enzymes: reverse transcriptase, protease,
• Integrase, inhibit fusion, inhibit viral translation
• No vaccine
• Prevention, monogamous sexual relationships, condoms,and universal precautions

AIDS
• First emerged in early 1980s
• HIV-1 & HIV-2 are not closely related
• HIV-1 may have originated from a chimpanzee virus
• 1959 first documented case of AIDS • HIV is found in blood, semen, & vaginal secretions.
• HIV is transmitted by sex, sharing needles, and mother to child.
• HIV does not survive long outside of the body.

Risk Factors for AIDS
-Homosexuals or bisexual males- 45%
-Intravenous drug users- 30%
-Heterosexual partners of HIV carriers-11%
-Unapparent or unknown risk-9%
-Blood transfusions are no longer a serious risk due to testing
-Congenital or neonatal- can be reduced with antiviral drugs
-Medical and dental personnel- 1/500 needle-stick

Poliomyelitis (Polio)
-Acute enteroviral infection of the spinal cord that can cause neuromuscular paralysis
-It is also called the infantile paralysis because it often affects small children
-Has a naked capsid that confers chemical stability and resistance to acid, bile, and detergents
-Virus survives gastric environment and other harsh conditions, which contributes to its ease in transmission
-Is more pronounced during the summer and fall
-Is passed within the population through food, water, hands, objects contaminated with feces, and mechanical vectors.

Diagnosis of Polio
Polio is mainly suspected when epidemics of neuromuscular disease occur in the summer in temperature climates. It can usually be isolated by inoculating cell cultures with stool or throat washings during early part of the disease. The stage of the patients infection can also be demonstrated by testing serum samples for the type and amount of antibody.

Treatment and Prevention of Polio
The mainstay of prevention is vaccination as early in life as possible, usually in 4 doses starting at about 2 months old. Adult candidates for immunization would be travelers and members of the army.
There are 2 forms of the vaccine currently in use, the inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV). Both are prepared from animal cell cultures, are trivalent and are effective.





THIS IS A LITTLE BIT MORE COMPACT VERSION OF WHAT WE NEED TO KNOW FOR CH 25 RNA VIRUSES

-False negative vs. false positive - try to minimize false negatives
-Phenylketonuria (PKU) - test babies for enzyme and if they can metabolize it
-Influenza
.....-enveloped
.....-antigens (spikes) change
..........-drift - minor
..........-shift - major
.....-harvard has a library of antibodies and one works well against the base of flu spikes rather that the tip of spikes
.....-w/in top 10 causes of death world wide
.....-respiratory transmission
.....-infect all sorts of things and can jump to different hosts ie. humans and bird flu
.....-fever, headache, throat pain, but NOT VOMITING
.....-classified by numbers
.....-becomes more and more resistant each year
.....-post war 1918-1919 20-40 million deaths
.....-25 times more leathal than normal
.....-10 times more deadly than the war was
-bird flu
.....-very close proximity to birds
.....-person to person, but never person to person to person
-Mumps
.....-uncommon
.....-German measles (Reubella)
..........-could cause birth defects
.....-regular measles
..........-white spots inside mouth
-Rabies
.....-enveloped
.....-effects brain and changes behavior
.....-don't want water
.....-can still get antibodies after infection
..........-only one like that
.....-most common in dogs
..........-look for dark inclusions in brain/spinal cord
-Retrovirus
.....-HIV
..........-comes in as RNA and goes to DNA and then inserts in to our DNA
.....-AIDS
..........-less than 200 T-cells per MM of blood
..........-attacks T-helper cells and macrophages
..........-destroys immune system and other illness kill you
-Polio
.....-fecal/oral - intestinal
.....-usually doesn't infect nervous system
.....-most people had it in the 1950's
-Hepatitis
.....-A and C - RNA
.....-B - DNA

Questions:

Q&A~~Home Page~~Top of Page

1. Which receptors of the influenza virus are responsible for binding to the host cell?
a. hemagglutinin
b. neuraminidase
c. type A
d. capsid proteins

2. The primary site of attack in influenza is the
a. small intestine
b. respiratory epithelium
c. skin
d. meninges

3. Which of these happens in the case of antigenic shift in influenza A?
a. single mutations in hemagglutinin
b. recombination of RNA segments between bird and human strains
c. change from influenza A to influenza B
d. both a and b

4. Infections with ______ virus cause the development of multi-nucleate giant cells.
a. rabies
b. influenza
c. pneumo
d. corona

5. Which virus is responsible for Korean hemorrhagic fever?
a. Ebola virus
b. hantavirus
c. arena virus
d. flavivirus

6. For which disease is an exanthem (skin rash) not a symptom?
a. measles
b. rubella
c. coxsackievirus infection
d. parainfluenza

7. A common, highly diagnostic sign of measles is
a. viremia
b. red rash
c. sore throat
d. Koplik's spots

8. Viruses that cause serious diseases in infants are ____ and _____.
a. mumps, calicivirus
b. respiratory syncytial virus, rotavirus
c. coxsackievirus, HTLV II
d. bunyavirus, cardiovirus

9. Rabies virus has an average incubation period of
a. 2 to 3 weeks
b. 1 to 2 years
c. 4 to 5 days
d. 1 to 2 months

10. For which disease are active and passive immunizations given simultaneously.
a. influenza
b. yellow fever
c. measles
d. rabies

11. Which of the following is considered to be the next pandemic?
a. mumps
b. avian influenza
c. measles
d. west Nile virus

12. Measles and the German measles are caused by the same virus Morbillivirus?
a. True
b. False

13. Which of the following is considered dangerous for infants and hospitals try to prevent?
a. Pneumonvirus
b. Morbillivirus
c. mumps

14. Which of the following has bullet-shaped virions?
a. RSV
b. Mumps
c. Influenza
d. Rabies

15. This animal is the most common carrier of rabies in the US...
a. dogs
b. skunks
c. foxes
d. raccoons

16. Polio and hepatitis A viruses are _______ viruses.
a. arbo
b. enteric
c. cold
d. syncytial

17. Which of the following cells is a target of HIV infection?
a. dendritic cells
b. monocytes
c. helper T cells
d. all of these can support infection