Micro: RNA Animal Viruses

BIOL 2421 Microbiology Lecture Notes: RNA Viruses Dr. Weis

Nucleic Acid	Capsid	Envelope	Biosynthesis	Family Name

ds RNA, segmented	Icosahedral	No	Cytoplasm	Reoviridae

ss + RNA	Icosahedral	No	Cytoplasm	Calciviridae
ss + RNA	Icosahedral	No	Cytoplasm	Picornaviridae
ss + RNA	Icosahedral	Yes	Cytoplasm	Togavirus
ss + RNA	Helical	Yes	Cytoplasm	Coronaviridae
ss + RNA	Helical	Yes	Cytoplasm	Flaviviridae
Ss + RNA	Star-like	No	Cytoplasm	Astrovirus

ss – RNA	Helical	Yes	Cytoplasm	Bunyaviridae
ss – RNA	Helical	Yes	Cytoplasm	Orthomyxoviridae
ss – RNA	Helical	Yes	Cytoplasm	Paramyxoviridae
ss – RNA	Helical	Yes	Cytoplasm	Rhabdoviridae
ss – RNA	Helical	Yes	Cytoplasm	Filoviridae
ss – RNA	Helical	Yes	Cytoplasm	Arenaviridae

2 ss + RNA	Icosahedral	Yes	Cytoplasm	Retroviridae

A universal system for classifying viruses has been established to make use of a series of ranked taxons that follow other similar taxonomic nomenclature.

Order (-virales) being highest currently recognized

Family (-viridae)

Subfamily (-virinae)

Genus (-virus)

Species (common name)

Replication of RNA viruses takes place in the cytoplasm (as indicated above)

Positive sense ss RNA genome is the same polarity as mRNA and is used to make the negative sense strand RNA, which in turn becomes the template for new positive sense RNA.

The negative sense ss RNA genome is used to generate positive sense ss RNA that serves as mRNA as well as a template for making more negative sense ss RNA.

The 2 ss positive RNA genome of the Retroviridae functions as a template for viral DNA by using reverse transcriptase (RNA-dependent DNA polymerase) to make the negative sense DNA strand, which is then used to make the complimentary DNA positive sense strand copy. Once the ds DNA is made, it will integrate into the host cell genome to prove the template for mRNA synthesis.

Double stranded RNA will act as templates for the opposite sense strand as well as making viral mRNA.

REOVIRIDAE

The name is derived from the phrase “respiratory enteric orphan viruses” infect the human respiratory and intestinal tracts. Over 150 member group. 10-12 segmented linear ds + RNA which contains 20-30 genes. Double to triple layer capsid, Icosahedral, nonenveloped family of viruses causing human disease are:

Colorado Tick Fever: causes encephalitis

Rotavirus Group A: acute infantile diarrhea, also known as winter gastroenteritis

Colorado Tick Fever:

Tick transmitted disease, Acute febrile illness, chills, nausea, headache, +/- rash

Virus can stay in the blood for up to 4 months

Treatment and prevention: remove tick; avoid tick infested areas, insect repellents

Rotavirus

Have three shells: Outer capsid, inner capsid, and core which surrounds RNA

Worldwide infection, major cause of death in third world countries

Stable in environment

Spread: fecal-oral ingestion, sewage contaminated water

Incubation: 1-3 days

Clinical Signs: sudden onset of watery diarrhea, disease is self limiting

Secondary complications of dehydration, especially in children

TX: replace fluid loss (diarrhea, +/- vomiting)

DX: EM, latex agglutination, ELISA

Prevention: hygiene, clean water, sanitation, developing a vaccine

CALICIVIRIDAE

The family name comes from the Latin word, caliculus, which means cup-shaped as these viruses have the appearance of a cup in the shape of a 6 pointed star. Nonenveloped, Icosahedral, linear ss + RNA coding for 4-6 genes. Very similar to Picornaviridae, only larger. Widely distributed and infection is common in children. There are five antigenic types. The ones causing human diseases are:

* Norwalk Agent: epidemic viral gastroenteritis, summer diarrhea

* Hepatitis E: endemic hepatitis, high mortality during pregnancy

Norwalk Agent

Gastroenteritis, vomiting with cramps, +/- diarrhea

Common source ingestion, occur in institutions and spread throughout households

Dx: none readily available, ID virus particle in stool

Hepatitis E

Non A – non B Hepatitis, endemic in developing countries

Incubation 30-40 days

Acute, self limiting hepatitis, no chronic carrier state

Virus replicates in gut, spreads to liver, shed in stool

Spread: Fecal contamination of water, large inoculum needed

Dx: IgM to HEV, ID virus particles in stool

PICORNAVIRIDAE

The family name comes from the Latin, pico, which means small and RNA denoting the type of nucleic acid. These are the smallest of the RNA viruses. Nonenveloped, icosahedral, ss + RNA. The members of this family that cause human disease are:

* Polivirus: infection in the anterior gray matter horns of the spinal cord

* Coxsackie A virus

^ herpangia: infection of oral mucosal cells

^ aseptic meningitis

^ common cold: URTI

^ epidemic myalgia: affects pleura and abdominal muscles

^ hand, foot, mouth disease: infection of epithelial cells of these regions

* Coxsackie B virus

^aseptic meningitis

^ epidemic myalgia

^ myocarditis

^pericarditis

* ECHOvirus

^ aseptic meningitis

^Boston exanthema

^ Cerebral ataxia

^ Rhinovirus: agent of the common cold

^ Hepatitis A: agent of infectious hepatitis

^ Mengovirus

Poliovirus

Poliomyelitis

Mild cases: fever, sore throat, nausea

Severe cases: paralysis

Stable virus in food and water

Transmission: fecal-oral contamination

Asymptomatic = 90%, Other phases: Abortive, Non-Paralytic, Paralytic

Paralytic polio accounts for 2-3% of polio infections, but 75% of spinal paralysis.

Virus multiplies in throat and small intestineà tonsils/ LN of neck and ileum à

Blood à CNS: multiplies in motor nerve cells in upper spinal cord, killing

Cells, resulting in paralysis à respiratory failure = death

Dx: Virus isolation from feces and throat secretions, cell culture

Prevention: Vaccination [IPV (Salk), E-IPV, OPV(Sabin)]

Hepatitis A

Infectious Hepatitis

Incubation period: 3-5 weeks

Milder disease than Hep B, asymptomatic infections are very common

No chronic form of the disease

Virus enters via the gut à replicatesà spreads to liver and multiplies in hepatocytes.

Symptoms: Anorexia, nausea, vomiting, pain (URQ), increased liver enzymes

Virus is excreted in stools for 2 weeks preceding onset of symptoms, therefore,

Enteric transmission, fecal – oral or contamination of water or food

DX: IgM

Prevention: Passive immunization, Vaccination is available, not widely used

Rhinovirus

Common cold virus: 50% of cases

Inhalation infection of the URT

Incubation period: 1-3 days

Symptoms: headache, sore throat, wateryà mucopurulent nasal discharge

Complications: predispose to secondary bacterial infections

TOGAVIRIDAE

The family name is derived from the Latin, toga, meaning coat. Icosahedral virion with a spiked envelope and a linear ss + RNA.

Taxonomy structure:

Genus Alphavirus

Genus Rubivirus

Alphavirus

* VEE, WEE, EEE [equine encephalitis]

* Sindbis: causes fever, rash, arthritis

* Semliki Forest: causes encephalitis

* Ross River: causes fever, rash, arthralgia

Rubivirus

* Rubella: agent of German measles

German Measles

Rubella

Respiratory spread, milder version of rubeola (measles)

Incubation 2-3 weeks, infection consists of facial rash and mild fever

Rash spreads to other areas of the body, changes hourly, disappear in 3 days

Transmission: droplet

Incubation: 2-3 weeks

Complication: congenital rubella syndrome

Maternal infection during first trimester = birth defects affecting

Nervous, special senses (eye, ear), and heart

Tx: supportive

Prevention: part of MMR (measles, mumps, rubella) vaccine

CORONAVIRIDAE

The name refers to the characteristic halo or crown which surrounds the virion. Enveloped, helical, ss+RNA that are the causes of the coronavirus human diseases:

* Common cold: 15-20% of cases

* SARS: severe acute respiratory syndrome

SARS

Transmission: respiratory droplet, direct and indirect

High fever and body achesà dry cough à pneumonia

Incubation period: 2-10 days

Virus can survive in environment for several days

Dx: PCR for Viral NA

Tx: supportive, treat for other viral respiratory infections

Prevention: avoid close contact, self-quarantine, disinfect areas

FLAVIRIDAE

The name is taken from the Latin, flavus, which means yellow as this refers to the fact that this is the family of the yellow fever virus. Enveloped, helical, ss + RNA group Includes family of flavivirus and pestivirus. Flavirus genus that cause human disease syndromes such as:

Hepatitis

Yellow Fever

Hepatitis G: nonA-nonB-nonC hepatitis

Acute, persistant infection, 0.3 % of hepatitis infections

Co-infection with Hepatitis C

Encephalitis

Japanese Encephalitis (JE) antigenic complex:

St. Louis, Japanese B, Rocio, Murray Valley, West Nile

Far Eastern Tick born

Kyasanur forest

Louping ill

Powassan

Kumlinge

Absetarov

Ilheus

Langat

Miscellaneous

West Nile: fever, rash, hemorrhage, shock

Dengue Virus: dengue fever

Omsk: hemorrhagic fever

St. Louis Encephalitis (primary one in U.S.)
acute inflammatory disease involving the nervous system

Vector Transmission: mosquito ; Reservoir: birds

Incubation period: 4-21 days

No Treatment, supportive care

Prevention: vector control, disinfection of areas

West Nile Virus (WNV) [recent "new comer" to U.S.]

Sudden onset of febrile illness lasting 3-6 days

Vector transmission: mosquito

Incubation: 3-14 days

Dx: IgM in serum or CSF via ELISA

Tx: supportive

Dengue Fever

Acute self limiting febrile disease

Headache, body pains, rash, hemorrhagic fever

Vector transmission: mosquitoes

Reservoir: primates, mosquitoes (in salivary glands)

Incubation period: 3-14 days (7 days average)

Tx: supportive care

Prevention: vector control, disinfect areas

ASTROVIRIDAE

The name of the family is derived from their appearance on EM, a smooth or slightly indented outer shell with inner 5-6 pointed star shaped core. They are nonenveloped viruses that contain ss+RNA. There are at least 7 human astrovirus serotypes which have a certain prevalence in different areas (Type 2 in Mexico, Type 6 in Japan, etc).

Human astrovirus 1 accounts for 70% of the viral disease which cause diarrhea.

BUNYAVIRIDAE

This group is named after the location of the initial virus isolation. Spiked Envelope, helical, circular ss – RNA that is spread by arthropods. Members of this family that cause human disease are:

Bunyavirus

* California encephalitis virus (LaCrosse virus): causes encephalitis

* Bunyamwera virus: causes encephalitis

Hantavirus

* Hanta virus: hantavirus respiratory syndrome

* Crimean-Congo hemorrhagic fever: causes hemorrhagic fever

Phlebovirus

* Sandfly river virus: fever, myalgia, retroorbital pain, conjunctivitis

* Rift Valley fever virus: causes hemorrhagic fever

Hanta virus

Adult respiratory disease: distress, SOB, myalgia, N/V, abdominal pain

Incubation: 1-3 weeks

Transmission: deer mice (rodents) via secretions (urine, saliva, droppings)

Reservoir: deer mice

Tx: supportive

Prevention: vector control, disinfect and clean rodent areas carefully

ORTHOMYXOVIRIDAE

The members of this family are all influenza viruses which reproduce in the mucous membranes of the upper and lower respiratory tract. Myxo is a Greek word meaning mucus. The viruses contain 8 segmented linear ss-RNA that is replicated in the nucleus. This family has helical symmetry associated with a neucleoprotien (NP) and a hemagglutin (for attachment and combine with specific RBC receptors) and neuraminidase spiked envelope creating a characteristic halo of projections around the virus particles. These envelope spikes are major antigenic determinants used to differentiate the various types.

H for hemagglutin (has 13 major antigenic types) and N for neuraminidase (has 9 antigentic types). Antibodies to the ribonucleoprotein (RNP) are used to differentiate between the influenza types. Members causing human disease are:

* Influenza viruses: type A, B, C: cause influenza [B & C are strictly human]

* Thogotovirus: causes encephalitis

Influenza is characterized by fever, myalgia, headache, pharyngitis. +/- cough. Usually not coryza (runny nose) that is characteristic of common cold infections. Range from mild, asymptomatic to moderate or very severe.

Reservoir: humans

Spread: droplet or fomite with inhalation into the pharynx or lower respiratory tract.

Incubation: 1-3 days

Replication: RNA is transported to nucleus and new viral proteins are made from Viral mRNA. Segmented RNA allows for the potential of recombinants to form if two different viruses infect the same cell, leading to new strains.

Complications: secondary bacterial infections by normal airway flora

Other viral superinfections (Adenovirus)

Dx: viral isolation from respiratory secretions, IFA, serology via agglutination

Influenza’s are named by

Type, Town, Number of isolates, year of isolation, Major HA and NA

Examples

Influenza A Hong Kong, 1968, H3N2 = Hong Kong Flu

Influenza A:

Essentially avian virus that has crossed into mammals.

Undergoes antigenic shift and antigenic drift

TX: Amantadine: may prevent influenza infection, high risk individ, not widely used

Now, newer treatments such as Tamiflu and Relenza are available. Block neuraminidase action.

Prevention: vaccines (70% protection) using Virus subunit. Examples of one influenza vaccine:

A/Singapore/6/86/(H1N1)

A/Johannesburg/33/94/(H3N2)

B/Beijing/84/93

PARAMYXOVIRIDAE

The members of this family are morphologically similar to the Orthomyxoviridae, but are larger. The exhibit helical symmetry, are enveloped with spikes (Hemagglutin, neuraminidase, fusion) and contain segmented linear ss – RNA containing 15-25 genes. Members of this family causing human disease are:

Paramyxovirus

* Parainfluenza virus: parainfluenza of upper and lower respiratory tract

Rubulavirus

* Mumps virus: infection of the parotid salivary gland

Morbillivirus

* Measles virus (rubeola virus): causes

~ Measles: infection of the mucosa and skin epidermal cells

~ Subacute sclerosing panencephalitis

* Rinderpest (cattle plague) : highly contagious, fatal disease in cloven-hoofed animals. Febrile state with oral ulcers, ultimately progressing to bloody diarrhea and death. (No, humans are not cloven-hoofed, so they don't get this diease. Just thought I would give you a taste of my world).

Pneumovirus

* Respiratory Syncytial virus: causes respiratory syncytial disease, croup

Parinfluenza

Large percentage of pediatric respiratory infections:

URTs, croup, bronchiolitis

4 types exist, Type 1, 2, 3 account for the majority of disease

Virus colonizes nose à nasopharynxà epitheliumà cilia lossà

Fibrinous exudate à continual cell damageà airway obstruction

And laryngeal muscle spasm

Low grade fever, runny nose (coryza), barking cough

Dx: no good test, possible viral culture

Tx: supportive care (steroids, bronchodilators)

Mumps

Tropism for glandular tissue

Transmission: respiratory/salivary droplet

Incubation: 21 days

Syndrome: febrile illness and inflammation of the salivary glands

Other complications

Aseptic Meningitis

Orchitis

Pancreatitis

Dx: IgM antibodies

Tx: symptomatic

Prevention: MMR vaccine, disease confers life long immunity

Measles

Highly infectious (80%)

Transmission: droplets = direct or indirect

Incubation: 10-12 days

Syndrome: epithelial tissue of upper respiratory tractà LN à blood

Causes inflammatory changes to skin, respiratory, gi that leads

to desquamation, skin also has a rash that begins to peel.

Prevention: MMR vaccine

Respiratory Syncytial Virus (RSV)

Most common cause of pneumonia in infants

Moderate to severe cold like symptoms: fever, coryza, cough, wheezing

If over 3 years of age, moderate symptoms. Can be more severe symptoms in younger patients

Transmission: respiratory secretions = direct, indirect

Increased incidence in closed, concentrated environments (day care)

Unstable in environment à survives a few hours, disinfect deactivates

Dx: IgM

Tx: symptomatic

Prevention: disinfection, hand-washing

RHABDOVIRIDAE

The family name is derived from the Greek word, rhabos, meaning rod-shape which refers to the bullet shape of this virus. There are over 200 rhaboviruses and they are enveloped with prominent spikes (G protein – hemagglutin), exhibiting helical symmetyr with ss – RNA. Members of this family that cause human disease are:

* Vesiculovirus

Vesicular Stomatitis : infection of the oral mucosa

Mild febrile illness in man

* Lyssavirus

Rabies virus: encephalitis

Transmission: Direct contact via wound or abrasion to skin

Replicates locally at injury site à ?LN--> PNS à CNSà

then back to Salivary glands.

Incubation: 3-8 weeks

Reservoir: foxes, bats, skunks. Others: dogs, cats, racoons.

Clinical Presentation

Furious Rabies: CNS irritability, excitement, hydrophobia, coma,

And death

Dumb Rabies: Lack of CNS excitement, paralysis, death

Dx: IFA, Negri bodies in brain neuron cytoplasm, virus isolation

Tx: Vaccination (inactivated- Human diploid) for at risk individuals

FILOVIRIDAE

The family name is derived from the filamentous form of the virus. These are spiked, enveloped viruses with helical symmetry. The virus outer shape is pleomorphic and can take on simple, filamentous, branched, circular, and U-shaped forms that are rounded at one end and have a distended swelling at the other. These viruses contain linear ss-RNA and are the most lethal of the human viruses since these viruses target vascular endothelium. Members of this family causing human disease include:

* Marburg Virus: acute hemorrhagic fever

* Ebola Virus: acute hemorrhagic fever

Incubation period: 4-16 days

Syndrome: Generalized aches with feverà vomiting/diarrheaàrashà

Hemorrhagic manifestations from open body cavityà death due to

shock associated with fluid and blood loss.

Virus avoids detection by immune system as virus has decoy truncated glycoprotein (SGP) that binds to neutrophils and interferes with their function causing immunosuppression.

ARENAVIRIDAE

The family name is taken from the Latin, arenosus, which means sand due to the sandy appearance of the riboprotein structure of the virion. The viral family is enveloped, helical, ss – RNA that consists of 2 segements (large and small) that form a circle via hydrogen bonding. There may be 2 nucleocapsids per envelope.

The genus arenavirus contains two subgroups:

* Old World arenavirus

Lassa virus

* New World arenaviruses

Lymphocytic choriomeningitis virus

Lassa Virus: fatal Hemorrhagic fevers

Transmission: rodent secretion = direct and indirect

RETROVIRIDAE

The name is derived from the fact that these viruses contain a reverse transcriptase (RNA-dependent DNA polymerase). This enzyme converts the RNA genome into DNA, which then integrates into the host chromosomal DNA. All human retroviruses infect CD4 bearing cells. This family contains all of the RNA containing tumor viruses and has a spiked enveloped, icosahedral capsid with 2 linear ss+ RNA.
This family has 7 genera that affect many different mammals, reptiles, and birds.

Human infections caused by members of this family include:

* Deltaretroviruses

Human T-Lymphotropic virus (HTLV): causes adult leukemia

* Primate Lentivirus

Human Immunodeficiency Virus (HIV, type 1 and type 2)

HIV-1: major cause of AIDS

HIV-2: lower virulence AIDS, confined to West Africa

* Spumavirus

Human Foamy (Spuma) virus: cryptic, no known pathology

HTLV-1

Aggressive tumor of CD4 lymphocytes which infiltrates the skin and brain

Tumors are produced after a long latent period

Transmission:

Horizontal = blood, sexual intercourse

Vertical = mother to child during breast feeding

HIV-1

See other notes for detail of viral replication and epidemiology