MYCV LEC - RNA VIRUSES AND PICORNA

Picornaviridae, Caliciviridae, Reoviridae

Naked RNA viruses

Picornviridae, Caliciviridae, Reoviridae, Retroviridae, Togaviridae, Flaviviridae (PCR RTF)

Icosahedral RNA viruses

Paramyxovirus

Largest RNA virus in terms of size

Picornaviridae

Smallest. Small positive strand RNA virus and does not have lipid membrane. (+) sense ssRNA, naked. Nucleocapsid that is about 30 nm in diameter. Largest in terms of family but smallest in terms of size. 5-10 hours of replication time.

Human parechovirus

HpeV 1 and 2 (both infects humans). Summer diarrhea

Ljungan virus

Zoonotic parechovirus

Parechovirus

Causes mild, gastrointestinal or respiratory illness, but have been implicated in cases of myocarditis and encephalitis. Usually asymptomatic but patient will confer immunity. Replication in lymphoid tissue of the pharyngeal space. Replication in intestinal wall. Target organs (CNS, muscles, heart, liver). Organ infection

Hepatitis A virus

ssRNA, (+) sense. Incubation 2-6 weeks. Infectious or epidemic hepatitis. Shed in the feces from two weeks before jaundice develops to about one weeks after jaundice. Easily develops an outbreak. Fever and jaundice. Acute self limiting infection. Chronic infection does not occur. Deaths occur rarely. Fulminant hepatitis. MOT: By mouth

Acute hepatitis A

Infection in children. Prodrome: Nausea, malaise, fever, joint pains. S/S: Juandice, dark urine, pale stools, tenderness of the upper right quadrant of the abdomen. Abnormal ALT.

Enterovirus

Isolated from the intestinal tract. MOT: By mouth, respiratory drops. Endemic worldwide. Very common infection in children. Incubation period: 3-35 days. 7-14 days. Shed in the feces for a long time. Most patients are asymptomatic but in children may cause benign fever, malaise, and fatigue.Accompanied by nonspecific rashes.

3 serotypes

Poliovirus species serotypes

34 serotypes

Echovirus species serotypes

22 serotypes

Coxsackie, group A species serotypes

23 serotpyes

Coxsackie, group B species serotypes.

4 serotypes

Enterovirus species serotypes

CD155

Expressed in spinal cord anterior horn cells. Dorsal root ganglia. Skeletal muscle. Motor neurons. Some cells of the lymphoid system.

Coxsackievirus receptor

Also binds adenovirus. Surface protein with 2 immunoglobulin like domains.

Poliovirus

Causes 21,000 cases of paralytic poliomyelitis in the US. Salk-inactivated. Sabin-attenuated. Most of the disease are from type 1 polio virus. Many children have symptomatic infections that lead to lifelong immunity.

Asymptomatic polio infection

Most common cases of polio. Occurs when replication is restricted to the GI tract. Characterized by mild fever with diarrhea to flaccid paralysis. Most cases end here.

Abortive poliomyelitis.

Minor illness. First symptomatic result is febrile disease. Occurs in the first week of infection. Patient may experience a general malaise which is accompanied by vomiting headache and sore throat. Occurs in 5% of infected individuals.

Nonparalytic poliomyelitis

3 or 4 days later, a stiff neck and vomiting as a result of muscle spasms may occurs in about 2% of patients. Virus has now progressed to the brain and infects the meninges. Targets the CNS.

Paralytic polio

About 4 days after the end of the first minor symptoms. Virus spreads from the blood to the anterior horn cells of the spinal cord and to the motor cortex of the brain. Degree of paralysis depends on the neurons affected. More pronounced in very young and very old patients.

Spinal paralysis

Commonly seen paralysis, small limbs. Targets the spinal cord. Causes complete flaccid paralysis of one or two limbs (either involves hands or feet).

Bulbar paralysis

Severe and fatal. Targets the cranial nerves and respiratory center. Paralysis on neck and respiratory muscles.

Post polio syndrome

This afflicts victims of an early polio virus infection but the virus is no longer present. It may occur many years after the infection and involves further loss of function in affected muscles perhaps a result of further neuron loss.

Coxsackie viruses

Most are never diagnoses precisely. Both types can cause paralytic disease or mild respiratory tract infection.

Coxsackie type A

Usually associated with surface rashes

Coxsackie type B

Causes internal symptoms. Bornholm disease

Bornholm disease

Upper RT infection that can result in fever and sudden sharp pains in the intercostal muscles. Pain in the abdomen and vomiting may be present. Incubation period: 2-4 days. Relapse is possible.

Meningitis

Enteroviruses are a major cause. Both A and B Coxsackie can cause aseptic ____. Characterized by headache, stiff neck, fever, and general malaise. Lymphocyte pleocytosis of the CSF is often observed. Most patients recover from the disease unless encephalitis occurs

Myocarditis

Coxsackie A and B can cause this in neonates and young children. Fever, chest pains, arrythmia, and even cardia failure result. High mortality rate.

Herpangina

Coxsackie virus A can cause fever with painful ulcers on the palate and tongue leading to problems swallowing and vomiting. Treatment of the symptoms is all that is required as the disease subsides in a few days.

Hand, Foot, and Mouth disease

This is an exanthem caused by E71. Symptoms include fever, and blister on the hands, palate, and feet. Subsides in a few days.

Rhinovirus

117 serotypes. Same with those of the enteroviruses but differs in acid-sensitivity and slightly denser. Common cold. Infects the mucosa of the nasopharyngeal space. Localized infection. Bronchitis or bronchopneuomonia. Superinfection with other bacteria. Occurs worldwide. MOT: Aerosol, mechanical. Primary site of infection: nasal epithelium. Virus may be detected in nasal washing. Undetectable by the fifth day. Characterized by rhinorrhea, nasal obstruction, sneezing, sore throat, and cough. Little fever and systemic reaction are uncommon. Illness may last for 1 week or more. May induce asthmatic attacks.

Common colds

Rhinovirus up to 30%. Coronavirus 10%. Adeno,Entero, RSV, Infleunza, Parainfluenza can also cause this indistinguishable from those caused by rhinoviruses and coronaviruses.

Virus isolation for Rhinovirus

Best isolated in human embryo lung fibroblast, or a sensitive continuous cell line. Identity can be confirmed by acid lability test.

Interferons

Proteins made and released by host cells in response to the presence of pathogens. Allows communication between cells to trigger the protective defenses of the immune system that eradicated pathogens or tumors.

Synthetic anti-rhinovirus

Could be used therapeutically and prophylactically

Arthropod-borne viruses (Arbovirus)

Group of viruses containing several families of arthropod-borne viruses. Transmitted through vector-borne transmission. Zoonotic viruses. Used to describe viruses from various families which are transmitted via arthropods. Mainly transmitted by means of an infected, blood sucking arthropod vector. Majority of are spherical. Few are rod shaped. 17-150 nm in diameter. Most are RNA genome except for ASFV.

Encephalitis

Infects neurons and CNS. Acute inflammation of the brain. Often results in fatal or irreversible damage of infected neurons. Transmitted by mosquitoes. May be caused by Togaviridae:

▪ Alphavirus (genera)

➢ Western Equine Encephalitis (WEE)

➢ Eastern Equine Encephalitis (EEE)

➢ Venezuelan Equine Encephalitis (VEE)

Flaviviridae

St. Louis Encephalitis

West Nile fever

Bunyaviridae

La crosse encephalitis

Rift valley fever

Undifferentiated fevers

Unknown or any group of illness resulting fro infection of any arbovirus which is pathogenic to human in which the only constant manifestation is fever. This fever can be accompanied by rash. Caused by Bunyaviridae and Reoviridae

Hemorrhagic fever

Systemic febrile disease with hemorrhaging, cardiovascular instability, hepatic, and renal insufficiency. Flaviviridae

→ Yellow fever

→ Dengue fever

Alphavirus

→ Chikungunya

Bunyaviridae

→ Crimean-Congo Hemorrhagic fever

Sylvatic cycle

Also known as the jungle cycle. Between arthropod and mammalian host in the wild. Dead end host is the one infected by the arthropod. Between arthropod and mammalian host with man. Infection ends in man. Many arbovirus possess this cycle

Urban cycle

Between domestic animals/man and arthropod species. Dead end host here is arthropod species

Yellow fever and Dengue fever

Both have sylvatic and urban cycle.

Flaviviridae

Size: 45nm. Enveloped. Icosahedral. (+) ssRNA. 3 Genera: Flavivirus, Hepacivirus, Pestivirus

Flavivirus

Name came from Yellow fever virus. Flavus meaning yellow. 40-65 nm. Average size: 45nm. Symmetry (enveloped, icosahedral nucleocapsid. Approximately 63 species.

Bunyaviridae

Size: 120 nm. Enveloped. Spherical or helical. (-) ssRNA. Largest family of mammal affecting viruses (250 viruses.) Arthropod borne or rodent borne vectors. Most are amplified in vertebrate hosts.

Bunyavirus

Causes Lacrosse encephalitis

Phlebovirus

Causes Rift valley fever

Nairovirus

Causes crimean-congo hemorrhagic

Tospovirus

Plant virus

Hantavirus

Causes hemorrhagic fever with renal syndrome. Hantavirus Pulmonary syndrome

Togaviridae

Size: 65 nm. Enveloped. Icosahedral. (+) ssRNA. Alphavirus (arthropod borne) Rubi (nonarthropod borne). Can agglutinate erythrocytes. Contains unique antigens and also share common antigens with other families. Protective antibodies are induced by the glycoproteins of the virus envelope. Transmission: bite of mosquito. Systemic infection involving viremia. Infect highly vascular organs. Invades central nervous system.

Alphavirus

Morphology: Spike-like structures on virion surface. Spikes are used to attach to susceptible animal cells. Transmitted by arthropods. Clinical picture varies.

Rubivirus

Rubella virus. Causes German measles. Not arthropod borne.

Reoviridae

Size: 70-80 nm. Enveloped. Helical capsid. dsRNA. Involved mainly in mild respiratory infections and infantile gastroenteritis. Reo (Respiratory Enteric Orphan Viruses). The capsid containing the RNA is digested upon entering the host cells. Genera: Coltivirus. Reovirus, Rotavirus.

Arbovirus encephalitis

Inflammation of brain tissue caused by a viral infection. Most common cause of viral encephalitis.

Acute viral encephalitis

Caused by viral infection of neural cells.

Post infectious encephalomyelitis

Follows infection with other viral agent + inflammation of brain tissue (encephalitis.)

Eastern Equine Encephalitis

Togaviridae - family. Alphavirus - genera. Caused by a virus transmitted to humans and horses by the bite of infected mosquito. Human cases occur relatively infrequently, largely because the primary transmission cycle takes place in swamp areas were population to be low. Incubation period: 4-10 days. Milder disease less common. Common manifestations: Fever, myalgia, headache, nausea, vomiting, abdominal pain and photphobia. Seizure and coma in severe cases.

Western equine encephalitis

Togaviridae - family. Alphavirus- Genera. Commonly associated with forage poisoning. Also known as cerebrospinal meningitis, corn stalk disease, harvest disease, sleeping sickness. Important cause of encephalitis in horses and prevalent in humans in North America, mainly in the western part of the US and Canada. Causes mild infection in people than in horses. Incubation: 5-10 days. Sudden onset of fever, headache, nausea, vomiting, anorexia, malaise. CNS signs in children less than 1 year old. Altered mental status, weakness, irritability, stupor, coma. 3% of individual die. 5-30% of young patients who survive have permanent neurological deficits.

Venezuelan Equine Encephalitis

Togaviridae - family. Alphavirus - genus. Also known as Peste loca or Derrengadera. Predominantly a problem in Central and South America, but it periodically occurs on the southern US. Its reservoir is small mammals and horses. Initial signs: 24-48 hours. Lethargy and anorexia can last 2-3 weeks. 4-155 of cases become neurological. Mortality rates less than 1%. In utero death.

La Crosse Encephalitis

Bunyavirus. Transmitted by tree-hole mosquito - vector. Incubation period: 2-7 days. Principal vertebrate hosts. Eastern vertebrate hosts (eastern chipmunks). Gray squirrels. Red foxes. Zoonotic pathogen that cycles between the daytime biting tree-hole mosquito and vertebrate amplifies hosts in deciduous forest habitats. More severe disease in children <16. Seizures, comas, paralysis, neurological sequelae. Death less than 1% of cases. Not often correctly diagnosed.

St. Louis Encephalitis

Flavivirus. Most common mosquito-transmitted human pathogen in the US. Leading cause of epidemic flaviviral encephalitis. Incubation: 4-21 days. Most cases asymptomatic. Less than 1% cases are clinically apparent. Clinically apparent or have manifestation/symptoms. 60% of patients have tremors. Milder disease in children. Elderly at highest risk for severe disease and death.

West Nile Virus

Flavivirus. First isolated in the West Nile Province of Uganda. Virus can infect people, horse, many birds, and some other animals-host. Majority are found in africa. Can cause acute flaccid paralysis. Most person develop West Nile poliomyelitis. Diagnosis is based on CS and PCR.

Japanese encephalitis

Flavavirus. Enveloped, single stranded RNA virus. Morphology not well defined. Incubation period: 6-8 days. Most asymptomatic or mild signs. Children and Elderly are both affected. Highest risk for severe disease. Mosquitoes: Culex species. Reservoir: Andreid (wading birds). Transmitted by culex mosquito, which breeds in rice fields. Mosquitoes become infected by feeding on domestic pigs and wild birds infected with Japanese encephalitis virus. Infected mosquitoes transmit virus to humans and animals during the feeding process.

Live attenuated vaccine

Used in equine and swine. Successful for reducing incidence.

Inactivated vaccine

Used for humans. Recommended for travelers visiting endemics areas of JE for >30 days

Colorado tick fever

Occurs in the Rocky Mountain states. Mild disease resulting in fever, headache, myalgia, and often accompanied by rashes. Transmitted by ticks. Caused by Reovirus. Manisfestation is like RMSF

Rift Valley Fever

Most spread by sandfly or Aedes species of mosquitoes. Zoonotic effect; causes abortion in livestock animals. Highly infectious by aerosolized blood. Immunization of livestock is the most effective way to control and prevent the disease. Febrile disease in humans. Targets the liver. Bunyaviridae, phlebovirus. Symptoms include: Fever, Encephalitis, Retinal vasculitis. Biological vector: sandfly

Dengue Virus

Most important vector borne viral disease. Single stranded RNA virus (+) ssRNA. Flaviviridae, Flavivirus. Small, 40-50nm spherical with lipid envelope. DEN1,2,3,4

Each serotype provides specific lifetime immunity, short time cross immunity. All serotypes can cause severe and fatal infections. Some serotypes appear to be more virulent. Man is the only known host. Arthropod borne. Primary vector: Aedes aegypti

Secondary vector: Aedes albopictus

4-7 days incubation. “Breakbone fever”

Usually affects older children and adults. Acute febrile illness of sudden onset. Petechiae and purpura are most common.

Aedes aegypti dengue virus

More effective in urban areas. Breeds close to man. Infected female transmits dengue virus. Primarily a daytime feeder. Usually found indoors. Outdoors, in clean rainwater.

Aedes albopictus

More effective vector in the rural areas. Breeds in areas of dense vegetation. Leaves are good receptacles of rain water.

Chikungunya virus

Transmitted to humans by virus carrying Aedes aegypti mosquitoes. Causes similar to dengue fever. Under Togaviridae, Alphavirus. Incubation 2-4 days. Fever up to 40c. Petechial or maculopapular rash of the trunk. Arthalgia or arthritis affecting multiple joints. Platelets: normal. Temperature: constant 40C. No specific treatment. No vaccine

Yellow fever virus

Caused by flavivirus, flaviviridae. Also known as Leprosia, Yellow jack, Black vomit, American plague. Important cause of hemorrhagic illness in many African and South american countries. Jaundice. Incubation period: 3-5 days. Only fever and headache are present. Toxic phase: fever, chills, bleeding into the skin, slow heartbeat, headache, back pains, extreme prostration. Coffee ground vomit. Jaundice appears on the second or third day. Replicates locally. High viral load in blood. Necrotic masses appear in the cytoplasm of hepatocytes. No true cure.

Caliciviridae

Described in 1976. HuCV, SRSV

Genome: ssRNA

Naked. Capsid: 30-45nm

Icosahedral

Has 32 cup shaped depressions

Describe as the “Star of David”

MOT-FOR

Enteritis, worldwide distribution, outbreaks can involve infants and school-age children

Outbreaks related to consumption of contaminated oyster and shellfish has been described. Seafood and ice also one contributory factor. Most people have had infection by the age 4 and below. Commonly known as “Winter Vomiting Disease”.

12 hours to 4 days

Most infection are asymptomatic

Mild diarrhea, vomiting anorexia and fever.

1/3 have respiratory symptoms. Specimen: Stool. EM, ELISA, Antigen assay

Human caliciviruses

HuCV, commonly infects humans.

Small, round structured viruses

SRSV, Norwalk virus

Astroviridae

Described in relation to an outbreak of gastroenteritis in 1975. Small ssRNA, naked. Capsid: 27-32 nm. Icosahedral

Round with unbroken surface. Appearance: “5 or 6 pointed star”. Immunologically distinct from Norwalk and Caliciviridae. Also causes infection on GIT.

7 human serotype. Diarrhea, headache, nausea, low grade fever, low level of pathogenicity. MOT-FOR. Worldwide distribution, mainly in children, 7 years of age. Fecal contamination of seafood or water. EM, IFT, No serologic tests.

Hantavirus

Family: Bunyaviridae

Spherical or oval shaped. Enveloped RNA viruses. More than 30 different Hantavirus species. Survives at 12 hours at 4C ref temp. High salt cone. Non physiological pH 1-3 days after drying. Emerging disease.

Via chronically infected rodent. Horizontal transmission of infection by intraspecific aggressive behavior. Virus is present in: Aerosolized excreta, throat swab and feces, mucous membrane contact, skin breaches.

From rodent to human: Breathing contaminated air, touching contaminated surface, bite from an infected animals.

Do not adversely affect their host.

Hosts will acquire life long chronic infection. Virus is shed through host saliva, urine and fecal matter, humans are infected by inhaling the virus from aerosols produced while host is excreting waste. Aerosols can occur by disturbing contaminated nesting materials.

Deer mouse

Hantavirus. Peromyscus maniculatus

Cotton rat

Hantavirus. Sidmodon hispidus

White footed mouse

Hantavirus. Peromyscus leucopus

Striped filed mouse

Hantavirus. Apodemus agrarius

Bank vole

Hantavirus. Clethriomomys glareolus

Rat

Hantavirus, Rattus

Hantavirus disease

Hantavirus antigen become disseminated throughout the blood stream. Loss of fluid from blood vessels

Hemorrhagic fever with Renal syndrome

Species known to cause disease are Dobrava, Hantaan, Puumala, and Seoul

Hantavirus Pulmonary Disease

Sin Nombre Virus - North America

More serious and rapidly progressive illness.

Stages of Hemorrhagic Fever with Renal Syndrome

After an incubation period of 1-2 weeks

1. Febrile phase

2. Hypotensive phase

3. Oliguric phase

4. Diuretic phase

5. Convalescent phase

   All phases lasts for 4-40 days

Febrile phase, HFRS

Persists for 3-5 days.

Sudden onset fever and chills. Headached, severe myalgia, nausea, blurred vision, photphobia, pain on ocular movement. Flushing of face. Petechiae, abdominal pain and back pain. Vascular leak syndrome

Vascular leak syndrome

Characterized by thirst, edema, hemoconcentration, postural hypotension

Hypotension phase, HFRS

Lasts for hours or days. Blood pressure decreases, hypovolemia, shock. Worsening of bleeding manifestations: Petechiae, epistaxis, gastrointestinal and intracranial bleeding.

Level of urea and creatine in blood rise. Proteinuria.

Oliguric phase, HFRS

Elevation of blood pressure

Hypervolemia leading to hypertension

Urine output decreases-increases blood volume

Blood electrolyte imbalance. Severe complications. Cardiac failure, pulmonary edema, cerebral bleeding.

50% OF fatalities occur during this phase.

Renal dysfunction

Recover, HFRS

Blood pressure normalizes, urine output normalizes.

Diuretic phase - Lasts a few days to a few weeks. Clinical recovery begins. 3-6 liters of urine/days. Anorexia, lassitude due to dehydration.

Convalescent phase - Lasts 2-3 months. Progressive improvement in glomerular filtration, renal blood flow, and urine concentrating ability.

Nephropathia Epidemica

Cause: Puumula strain

Most common form of HFRS in europe

Milder form of HFRS

Similar sequence of symptoms but attenuated.

Only 6% of serologically conformed cases require hospitalization

Stages of Hanta pulmonary syndrome

After asymptomatic incubation of

1. Febrile phase

2. Cardiopulmonary phase

3. Diuretic phase

4. Convalescent phase

Febrile phase, HPS

Flu like symptoms.

Lasts 3-5 days (1-12 days)

Fever, myalgias, malaise

Headache, dizziness, anorexia, nausea, vomiting, and diarrhea.

Difficult to diagnose at this phase

Cardiopulmonary phase, HPS

Non-productive cough and tachypnea (rapid breathing). Presentation and rapid progression of shock and pulmonary edema (4-24 hours).

Hypovolemia due to progressive leakage of high protein fluid from blood to lung interstitium and alveoli. Myocardial failure. Hypotension and oliguria - urine output decreases to conserve blood.

Death within 24-48 hours due to hypoxia and circulatory compromise. This phase causes death as blood goes to the lung interstitium, making it difficult to oxygenate the body.