VIROLOGY

• Small obligate intracellular parasites Viruses vary widely in size and structure.

• All viruses enter living cells, and once inside, use the cell to make more copies of the virus.

• VIRION: Complete virus particle : nucleic acid + protein coat, which may be surrounded by an envelope

• It is the form in which the virus moves between cells or hosts

• Bacteriophage are viruses that infect bacteria.

• Nucleic acid• Capsid

• Viral envelope

Classification Of VirusesAccording to•

1- Genome: DNA or RNA _-this could be either SS or DS • 2- Capsid: made of A capsomeres 3 types of capsid symmetry

symmetry:• Cubic (icosahedral) • Helical

• Complex• 3-Envelope: made of lipids• proteins and carbohydrates.• Viruses could be enveloped• or non-enveloped.• 4- Host range: Infect specific• types of cells in specific host.• animal, plant, bacterial.• Bacterial viruses are called bacteriophage

Viral Replication- When a virus infects a cell, nucleic acid must be uncoated and gain

access to metabolic machinery of cell. - Steps of Viral replication cycle: • attachment

• penetration, with entry of .nucleic acid into cell • early expression of virus genes (either directly by translation, if

virus contains "+" RNA, or indirectly after transcription and then translation)

• replication of virus nucleic acid • synthesis of new virion components • packaging and assembly of new virions • exit from cell

Transmission Of Viral Infection

• Enveloped Viruses: sensitive to harsh environments. They tend to be transmitted by respiratory, Parenteral or sexual route.

• Non-enveloped viruses are more stable and often transmitted by fecal oral transmission.

Viral Infection• Once the virus is inside the host cell, two• different processes may occur.• 1- Lytic Infection• Lytic Infections are caused when the virus• invades a host cell, makes copies of itself, and• eventually causes the cell to burst.•

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2- Lysogenic Infections• occur when a virus finds a receptor site on a host cell and• injects its genetic material into the host.• - Rather than immediately manufacturing the new viral DNA, the host cell incorporates the viral

DNA(prophage) into its own DNA.• - When the host cell replicates or divides, the extra DNA acts just like an inert segment of DNA.• • It causes no harm to the host• • However, externaLstimuli can trigger the "extra DNA" to become virulent.

Antiviral Chemotherapy Targets in the life cycle of viruses Attachment1- Using agents which mimic the virus-associated protein (VAP) and

bind to the cellular receptors. This may include VAP anti-idiotypic antibodies, natural ligands of the receptor and anti-receptor antibodies.

2-Using agents which mimic the cellular receptor and bind to the VAP. This includes anti-VAP antibodies, recepor anti-idiotypic antibodies extraneous receptor and synthetic receptor mimics.

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• A. Attachment of virus to receptor on host cell membrane. • B. Antibody prevents adsorption of virus

Antiviral ChemotherapyUncoating• Amantadine and rimantadine , have been introduced to combat influenza. These

agents act on penetration /uncoating.• PleconariI works against rhinoviruses,

which cause the common cold, by bocking a pocket on the surface of the virus that controls the uncoating process.

• Virus replication and synthesis Nucleic acid replication

1-Nucleotide or nucleoside analogues that look like the building blocks of RNA or DNA, but deactivate the enzymes that synthesize the RNA or DNA once the analogue is incorporated.

E.g. acyclovir against herpesyirus infections, e.g. zidovudine (AZT) against HIV.

2-Integrase Inhibit integrase enzyme that splices the

synthesized DNA into the host cell genome.

Viral synthesis:- 1- inhibition of transcription

2- Translation inhibition by antisense. 3- Assembley inhibition by protease inhibitors Release Two drugs named zanamivir (Relenza) and oseltamivir

(Tamiflu) that have been recently introduced to treat influenza prevent the

Release of viral particle moleculenamed neuramindase that is found on the surface of flu viruses, and also seems to be constant across a wide range of flu strains.

• Immune system stimulation

1 - Interferons• Inhibit viral synthesis in infected cells. One form

of human interferon named "interferon alpha" is well-established as part of the standard treatment for hepatitis B and C.

• 2-Monoclonal antibodies used against Respiratory Syncytial Virus in children.

Viroids Plant pathogen : consist of single-stranded RNA without the protein

coat that is typical for viruses. Prions - Infectious particles that are entirely protein. - No nucleic acid -Highly heat resistance -Animal disease that affects nervous tissue -Affects nervous tissue and results in Bovine spongifonn encepahltits (BSE) "mad cow disease", scrapie in sheep kuru & Creutzfeld-Jakob Disease (CJD) in humans «•

Medically Important Viruses • Herpes Simplex virus infections• Hepatitis• Childhood viral diseases• Heamoragic viral infections• Food born viral infections• Influenza• AIDs

Herpes Simplex Viruse

• Enveloped large double-stranded, DNA encased withinan icosahedral capsid virus. '

• Two strains HSV-1, HSV-2. Infection

HSV-l causes cold sores or fever bilsterswhereas HSV2 is more often associated with genital herpes

• An infection by a herpes simplex virus is marked by watery blisters in the skin or mucous membranes of the mouth, lips or genitals. Lesions heal with a scab.

• After the initial, or primary, infection, HSV becomes latent in the cell bodies of nerves in the area. Some infected people experience sporadic , episodes of viral reactivation, followed by transportation of the virus via the nerve's axon to the skin, where virus replication and shedding occurs.

Transmission • Horizontal transmission iLclose contact with an infected person who is• shedding virus from the skin, in saliva or in secretions from the genitals.• Vertical transmission of HSV may occur between mother and child during

childbirth causing encephalitis, which can be fatal to the infant, but the risk of infection is reduced if there are no symptoms or exposed busters during delivery.

Treatment• The antiviral most commonly used is Acyclovir or Valacyclovir.• Diet: Research has also shown that the virus's growth is to a moderate

degree proportional to the ratio of the aminp acid arginine to the amino acid lysine in the diet of infected individuals. A diet that is high in lysine and low in arginine is recommended for people suffering from regular outbreaks of HSV infections, because lysine interferes with arginine metabolism that is required for HSV- replication.

Child hood Viral DiseasesChikenpox

• Chickenpox (varicella) is an infectious disease caused by the varicella-zoster virus

• Transmission: both direct skin-to-skin contact and via respiratory droplets (coughing, sneezing) from the infected individual.

• IP is 14-16 days, and the first sign of disease is a asp? People are considered contagious for 2-5 days Before the onset of skin lesions and for 6 days after the last series of rashes have appeared.

Complications: • The most common complication is infection the lesion

with bacteria.• Rare complication include" pneumonia or encephalitis.

Children who have weak immune systems, eczema, or recent sunburns have more severe symptoms.

• Reactivation: Because the virus remains resting (latent) in the parts of nerves that are near the spinal cord (nerve roots) for life, about 1 in 10 adulte will get shingles (zoster) when the virus reappears, usually under conditions of stress to the body.

Hepatitis Viruses VIRUS Structure Transmission

Hepatitis A virus PICORNA, SS , non enveloped,RNA

Oral-fecal

Hepatitis B virus DNA virus Parental ,Sexual

Vertical

Hepatitis C virus RNA virus Parental

Hepatitis D virus RNA virus, SS

Code for one protein (delta antigen nucleocapside is enclosed within an envelope that carry HBs Ag

Parental

Vertical

Hepatitis E virus RNA , SS, non enveloped Oral –fecal water born

Hepatitis G virus RNA co-infection with Hepatitis C

Parental

Vertical

Viral Hepatitis Hepatitis B• Structure• Hepatitis B virus (HBV) is a member of the

Hepadnavirus family. It is an enveloped DS DNA with an icosahedral nucleocapsid core. The outer envelope carries the highly immunogenic surface antigen (HBsAg) which is involved in viral binding of, and entry into, susceptible cells.

• The virus is present in all body fluids

Hepatitis B Pathogenesis

Infections1- Acute infection with hepatitis B virus is associated with acute viral

hepatitis - an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, dark urine, and then progresses to development of jaundice. The illness lasts for a few weeks and then gradually improves in most affected people. A few patients may have more severe liver disease (fulminant hepatic failure), and may die as a result of it.

2- The infection may be entirely asymptomatic and may go unrecognized.

3- Chronic infection with hepatitis B virus may be either asymptomatic or may be associated with a chronic inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years. This type of infection dramatically increases the incidence of hepatocellular carcinoma (liver cancer). Chronic carriers are encouraged to avoid alcohol as it increases their risk for cirrhosis and liver cancer.

Transmission

Unprotected sexual contact, blood transfusions, re-use of contaminated needles & syringes, and vertical transmission from mother to child during childbirth.

• Diagnosis of Hepatitis B:-

• Detection of Hepatitis B surface Ag

• Detection of antibodies against Hepatitis B surface Ag

• Detection of Hepatitis B core Ag

• Detection of antibodies against Hepatitis B core Ag

Clinical Outcome Of Acute Hepatitis B

Hepatitis B Prevention

HBsAg VACCINATION • a Recombinant vaccines, and plasma-derived vaccines are used; • The two types of vaccines are equally effective and safe. Infants may

be vaccinated at birth.• a Infants for infected mothers maybe immunized by antibodies to the

hepatitis B virus (hepatitis B immune globulin or HBIg) as well. Treatment• b Treatment is used for patients suffering from fulminant hepatitis or

chronic hepatitis or immunocompromised . to reduce the risk of cirrhosis and liver cancer.

• a Acute hepatitis B infection doe^flotjusualjy require treatment• because most adults cleajjfte infection spontaneously. a Antiviral drugs

and interferon alpha-2a:

Hepatitis A

Structure• The Hepatitis virus (HAV) is a Picornavirus; it is non-enveloped and

contains a single-stranded RNA packaged in a protein shell.

Infections and Pathogenesis •HAV infection does not lead to chronic or persistent hepatitis. •Following ingestion HAV enters the bloodstream through the epithelium of

the oropharynx or intestine. The blood carries the virus to its target, the liver, and multiplies within hepatocytes and Kupffer cells (i.e., liver macrophages), Virions are secreted into the bile and released in stool; HAV is excreted in large quantities approximately 11 days prior to appearance of symptoms or anti-HAV IgM antibodies in the blood.

•The incubation period is 15-50 days. •Mortality is less than 0.5%.

Diagnosis of Hepatitis A • Detection of HAV-specific IgM • Hepatitis A virus is present in the blood, (viremia), and feces of

infected people up to two weeks before clinical illness develops.

Prevention• 1- Vaccination: The vaccine protects against HAV in more than 95%

of cases for 10 years. It contains inactivated Hepatitis A virus providing active immunity against a future infection.

2- Good hygiene and sanitation. Treatment• There is no specific treatment for hepatitis A. Sufferers are advised

to rest, avoid fatty foods and alcohol, eat a well-balanced diet, and stay hydrated.

Other Viral Hepatitis HepC: majority of people are subclinical, 25% of infected people develop acute

hepatitis some of these develop liver cirrhosis and some of these develop hepatocellular carcinoma.

• • Lab diagnosis: RT-PCR of viral RNA in blood of patients , antibody detection.

• • Treatment; Interferon a and the antiviral drug ribavarin. Hep D: Co infection with HepB.• Its presence with HepB results in fulminant hepatitis, and in case of chronic

hepatitis it results in liver cirrhosis and cancer.• Lab diagnosis: detection of delta antigen or IgM, or HDV in the serum• of patients. Treatment: no vaccine follow HBV. HepE.• Infects mainly young adults and is sever in pregnant women, can lead• to her death. No cnronicity.• Lab Diagnosis: viral RNA detected in feaces of infected patients. No

treatment and no vaccine

Childhood viral diseases Measles (rubeola) - Highly contagious infection of die respiratory system that is caused by a virus. a - - Measles virus is Enveloped, SS, negative-sense RNA viruses. - Transmission: aerosol transmission. - IP. about 10 days. 3 or 4 days of fever, cough cold-like symptoms followed by a ,

rash recovery after 2 weeks of illness and life-long (immunity) to becoming infected again.

• Complications from measles more commonly occur in children aged younger than 5 and adults older than 20. Serious complications of measles include blindness, inflammation of the brain caused by infection (encephalitis), sever dehydration, ear infections, and severe respiratory infections. The most common cause of death associated with measles is from pneumonia. SSPE is a rare chronic, progressive encephalitis .A history of primary measles infection usually before the age of 2 years followed by several asymptomatic years (6-15 on average) and then gradual, progressive psychoneurological deterioration, consisting of personality change, seizures, myoclonus, ataxia, photosensitivity, ocular abnormalities, spasticity, and coma. 1 jn 100,000 people infected with measles develop SSPE.

• No treatment only antipyretics .

German Measles(Rubella)

• Virus: enveloped icosahedral SS RNA.• IP 14-21 days followed by a• rash accompanied by fever 1-7 days• later.• German measles is usually a mild illness. However, if a

pregnant woman becomes infected, German measles can cause Congenital rubella syndrome: deafness, cataract and Congenital heart disease

• If the infection occurs 0-12 weeks after conception, there is a 51% chance the infant will be affected. Problems rarely occur when rubella is contracted by the mother after 20 weeks of pregnancy.

• Vaccination against rubella:-

• MMR vaccin living attenuted vaccine against rubella, measles and mumps

V

Influenza virus

•SS, RNA Enveloped ,spherical virus that has its genome segmented into(&segments )

•Envelope carry two types of antigens :H(heamagglutinin), N (neuraminidase). Variation in the Hand N results in antigenic shifts.Transmission by respiratory droplets

Pathogenesis Acute disease that is characterized by:chills, headache, extreme drowsiness, muscle aches andfever.

Complications:• pneumonia for the young and elderly or the immunocompromised.• Reye syndrome: vomiting, brain dysfunction, coma and death . This syndrome was

related to the use of aspirin as antipyretic. Most affected are teenagers and children.

Treatment: • amantadine, rimantadine prevent (inhibitors of

uncoating). • Relnza and Tamiflu prevent release of the

virus from infected cells (inhibitors of release). Prevention:• vaccine made of formalin inactivated virus and

should contain the specific subtypes of the influenza virus.

• Amantadin and rimantadin can be used as preventive medication for risk groups.

Human Immune Deficiency Virus (HIV)

-Enveloped SS RNA icosahedral virus that contain reverse transcriptase_enzyme that converts RNAto DNA.

Pathogenesis:• pathology results from tissue destruction by the virus itself , or the host response

to_the virus jnfected cells. HTV can induce a state of immunediffeciency that leads to opportunistic infection, Treatment:

treatment regimens and immune supperssion can havs serious effect on

on gastrointestinal health. Cachexia (wasting syndrome) and diarrhea are a hallmark of AIDS.

HIV Virus

AIDS : Acquired Immune Deficiency Syndrome Stages in the HIV infection • Category A: asymptomatic or swollen lymph nodes. • Category B: persistant infections by Candida albicans

in mouth throat and vagina, Shingles, persistent diarrhea, fever, cancerous or precancerous cervix. This is a latent period that would last for months to years.

• Category C : Clinical AIDS Candida of esophagus, bronchi, lungs, CMV eye infection pneumocystis pneumonia, toxoplasmosis, Kaposi's sarcoma.

Progression to AIDS takes about 10 years in adults.

HIV Virus

Diagnosis: • 1- CD4Tcells/mm3 a count below 200/mm3 is considered diagnostic. • 2- seroconversion • 3- Plasma viral load tests. Treatment: Highly active retroviral therapy HAART Prevention: • education • No vaccine due to (high mutation rate\ • Treatment of pregnant mother and newborn, screening blood supply, strict

adherence to standard precautions by health workers.

Rabies Virus

SS, RNA,enveloped helical symmetry Bullet shaped virus.

Transmission:

1- bite of a rabied animal

2-Aerosols from droppings of bats.

Symptoms: Hallucination , seizures ,

weakness,paralysis,coma ,finally death hydrophobia.

Once symptoms begins death is inevitable.

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Pathogenesis of Rabies

Treatment and prevention: •If clinical symptoms appear there is ineffective

treatment. •HDVC: Human Diploid Cell Vaccine preexposure

prophylaxis for people at high risk. •Postexposure prophylaxis after the animal bite: Clean the wound, passive immunization(RIG). Active immunization (vaccine).

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Arbovirus(Arthropod borne viruses)

Transmission: through bite of mosquito.

-The virus can replicate in both humans and mosquito -Mosquito bite is followed by viremia resulting in the

dissemination of the virus in target organ.Majority of infections are subclinical but some show differentclinical syndromes:

- Encephalitis e.g. Japanese encephalitis virus JEV. - Hemorrhagic fever e.g. yellow fever - Fever myalgia and rash e.g. dengue virus (dengue hemorrhagic

fever) Lab diagnosis: serologic acute and convalescent samplesPrevention: control the vector (Aedes aegypti) for dengue and yellow

fever. Vaccine for JEV"and yellow fever exist.

Rift Valley Fever

• Rift valley fever (RVF) is a viral zoonosis that primarily affects anjmals but also has the capacity to infect humans.

• Infection can lead to high rates of disease and death in animals and humans.

• Disease also results in significant economic losses due to death and abortion among RVF-infected livestock.

Rift Valley Fever

Transmission: - Direct contact between humans and blood or organs of infected

animals. Virus enters human body through: 1- inoculation through broken skin. 2- inhalation of earosoles3uring slaughtering of infected animals. 3- Ingestion of unpasteurized or uncooked milk. 4- Bites of infected mosquitos (mostly Aedes aegyptis) No human to Human transmission has been documented. No evidence of RVF outbreaks in Urban aereas.

Rift Valley Fever

Pathogenesis: - IP 2-6 days - Subclinical or mild : feverish syndrome with sudden onset of flu-

like symptoms, muscle pain, joint pain and headache. -Some patients develop neck stiffness, sensitivity to light, loss of

appetite (the disease may be mistaken for Other forms of the disease: ocular form, menigioencephalitis form, hemorrhagic fever form.

Diagnosis: IgM detection , cell culture, antigen detection by RT-PCR.

Treatme&prevention: symptomatic inactivated vaccine,

Rota virus

-DS RNA non-enveloped it has the appearance of a wheelTlnere are different strains of rotavirus and multiple infections by different strains occur.

-It is the most common cause o^severe diarrheajamong infants and children throughout the world and causes the death of about 600,000 children worldwide annually.

-Most children become infected with rotavirus by a^e 3^'

Transmission(Fecal oral.infectious particles are stable and can survive for long periods on surfaces

• Lab diagnosis:(Elisa& EM) for stool

Pathogenesis: IP is 48 hours. Infection could besubclinical or result in mild diarrhe and vomiting tosever non-bloody watery diarrhea that is accompaniedfever and vomiting dehydration and loss ofelectrorytes.

Treatment and Prevention •Rapid and efficient replacement of electrolytes and fluftfs that could

be sometime •Rotavirus vaccine that is live attenuated vaccine

Enteroviruses• SS RNA non-enveloped viruses Transmission : Fecal-Oral. -Stable in the low pH of the stomach, replicate in the gastrointestinal

tract and is excreted in the stool of patients. - Leave the GIT to the blood stream and spread to various organs. enterovjruses can cause CNS diseases they are major causes of

aseptic meningitis.-Viral meningitis occur mainly in summer and fall.- Affect both children and adults.

Treatment: Symptomatic. No antiviral Poliovirus is an enterovirus. -Prevention is(by vaccination)

-Vaccines : attenuated(Sabin), or killed(Salk)

Common cold viruses

Viral upper respiratory tract infection• is a self-limited contagious illness• that can be caused by any of 200 different types of viruses. Because of this

the body never builds up resistance against all of them. Thus colds are a frequent and recurring problem.

• Symptoms: runny_nose or scratchy throat fever and headache. Symptoms last for 10 days.

• Transmission: direct hand-to-hand contact with infected secretions or from contaminated surfaces.

• Pathogenesis: virus replicate at nasal passages because it requires lowtemperature.

• Treatment: Supportive measures for the common cold include rest anddrinking-plenty of fluids. Over-the-counter medications such as throatlozenges throat sprays, cough drops, and cough syrups may also helpbring relief Decongestants such as pseudoephedrine (Sudafed) orantihisiamines may be usect-for nasal symptoms. Saline sprays and ahumidifier may also be beneficial.