Viruses - RNA (-) sense Flashcards
NEG sense RNA
shared replication MOA
POS sense RNA replication MOA
- Viral RNA structure is complementary to hosts mRNA
- NEG sense ssRNA viruses bring their own RNA polymerase (vs. POS sense that only need the hosts RNA polymerase) → forms POS sense RNA to act as mRNA
- ALL RNA NEG (and all RNA POS) replicate in the cytoplasm EXCEPT Orthomyxovirus which replicates in the nucleus!!!
What are the 4 segmented NEG sense RNA viruses?
B.O.A.R. mnemonic
- Bunyavirus (3)
- Orthomyxovirus (8)
- Arenavirus (2)
- Reovirus (avg = 11; 9-12)
*** Segments are places where mutations can occur ***
(Antigenic drifts and shifts etc)
ALL the RNA viruses in sketchy videos replicate in the cytoplasm except?
Orthomyxovirus
Replicates in the nucleus!!!
ALL the RNA viruses in sketchy videos are SS except?
Reovirus
is DS!!!
Antigenic Drift vs. Antigenic Shift
- Antigenic Drift
Point mutation in the viral genome → can lead to changes in molecules like hemagglutinin (HA) or neuraminidase (NA) → usually causes endemics (like seasonal flu)
- Antigenic Shift
Segments (like HA or NA) are shared to form a new species → can lead to epidemics and pandemics (like swine flu antigenic shifted from humans, avian, and swine influenzas)
Otrhomyxovirus (Influenza)
lab tests
Night Shift at the Orthodontist’s
NEG** sense _S_S RNA**
Enveloped virus
8 Segments (B.O.A.R. mnemonic)
Otrhomyxovirus (Influenza)
3 main influenza viruses strains
*** Most common cause of the flu!!! ***
Night Shift at the Orthodontist’s
Strains A,B, and C
- Influenza A causes epidemics and pandemics (Antigenic shift, and drift)
- Influenza B causes endemics (Antigenic drift)
Otrhomyxovirus (Influenza)
signs and symptoms
Night Shift at the Orthodontist’s
- Myalgia, fever, and non-productive cough for about 7 days
- After it gets a little better can get pneumonia (common complication of influenza).
- Pneumonia usually from Staph aureus, but can be from others and includes symptoms of pneumonia, fever, and productive cough.
Otrhomyxovirus (Influenza)
Source
Night Shift at the Orthodontist’s
Spread by respiratory droplets
Main flu season in U.S. is from DEC → FEB
Otrhomyxovirus (Influenza)
MOA
Night Shift at the Orthodontist’s
- Influenza hemagglutinin (HA) is a glycoprotein found on the surface of influenza virus.
- HA binds to sialic acid on the cell membranes in the hosts URT and RBC’s.
- Virus is endocytosed into the cell after binding
- low pH activates the Matrix-2 (M2) protein channel to bring protons into the virion core
- pH change allows HA to faciliate fusion of the viral envelope with the hosts endosome membrane
- Virus uncoats, releasing the viruscontents, including its RNA genome, into the cell’s cytoplasm
Otrhomyxovirus (Influenza)
VF
Night Shift at the Orthodontist’s
- Hemagglutinin (HA) antigens (H1, H2, H3… H18) define cell tropism (cells that can be affected)
Humans can make anti-HA antibodies to protect from the same strain in the future.
- Neuraminidase (NA) cleaves the sialic acid inside the host cell allowing the virus to break free.
Otrhomyxovirus (Influenza)
Treatment
Night Shift at the Orthodontist’s
1) M2 protein inhibitors (Amantadine, Rimantadine)
- Inhibits uncoating, but allows ↑ dopamine release in CNS
- Older drugs, high resistance, only works against Inf. A
2) NA inhibitors (TamV/Tamiflu AKA Oseltamivir/Anamivir)
* Block release of the virus
Otrhomyxovirus (Influenza)
Vaccines
Night Shift at the Orthodontist’s
Get vaccine in October so have time to build an immune response before flu season (DEC → FEB)
1) Killed virus (IM)
- 2 forms of killed vaccine. Trivalent (2A + 1B) and quadravalent (2A + 2B)
- Children can get this vaccine after 6 months
2) Live vaccine (nasal spray)
Otrhomyxovirus (Influenza)
Influenza associated syndromes
Night Shift at the Orthodontist’s
- Pneumonia: (common complication) usually from Staph aureus, but can be from others and includes symptoms of pneumonia, fever, and productive cough.
- Reyes syndrome: Aspirin tx can cause encephalitis and hepatomegaly, liver failure, fever, rash, and vomiting by uncoupling (OX PHOS) mitochondrial proton gradient on ETC in the hepatic cell mitochondria.
- Guillen Barre syndrome: ascending paralysis with high protein in CSF and low WBS (albuminocytologic dissociation, an increase in the protein concentration of cerebrospinal fluid without an accompanying increase in the number of cells )
Paramyxovirus Family
lab tests
Paranormal Mixer
NEG** sense _S_S RNA**
Enveloped non-segmented virus
Anti-measles antibodies in the CSF (SSPE from Measles) or Warthin–Finkeldey cells in lymphoid tissue (for Measles/Rubeola)
Syncytia (cells merged together from RSV)
Steeple radiographic sign on xray (for Parainfluenza)
Paramyxovirus Family
Viruses in the Paramyxo family
Paranormal Mixer
*** Respiratory droplet transmission! ***
- Measles (Rubeola) AKA 1st disease
- Mumps
- Respiratory Syncytial Virus (RSV)
- Parainfluenza
Paramyxovirus Family
VF for each Paramyxovirus
(HA, NA, or Fusion proteins)
Paranormal Mixer
- Measles (Rubeola): HA & Fusion (no NA)
- Mumps: HA, NA, & Fusion
- Respiratory Syncytial Virus (RSV): Fusion (only)
- Parainfluenza: HA, NA, & Fusion
Measles (a Paramyxovirus)
signs and symptoms
Initial infection
AKA: Rubeola, 1st disease
Paranormal Mixer
- Prodromal (early) symptoms (4 C’s!!!): include Cough, Conjunctivitis, Koplic signs (blue spots on red near molars on bucal mucosa), Coryza (runny/stuffy nose)
- Fever of 104º F (40º C)
- 1-2 days later, after Koplic spots, a late maculopapular rash starts on head and works down (like rubella), but is a confluence rash (vs. rubella which does not coalesce)
- Complications including viral or bacterial pneumonia
Measles (a Paramyxovirus)
signs and symptoms
Persistent infection
AKA: Rubeola, 1st disease
Paranormal Mixer
Subacute sclerosing panencephalitis (SSPE)
AKA Dawson disease
- Rare and chronic form of progressive brain inflammation
- 1-15 years after initial Measles (Rubeola) infection
- Symptoms include personality changes, seizures, myoclonus, ataxia, coma, and possibly death.
- Buzzwords: “Measles as a child” or “Immigrants”
Measles (a Paramyxovirus)
VF
AKA: Rubeola, 1st disease
Paranormal Mixer
- Hemagglutinin (HA): causes RBC to stick together
- Fusion proteins: Causes multinucleated giant cells and red (eosinophilic) inclusion bodies → found in lymphoid tissue (AKA Warthin–Finkeldey cell)
*** NO Neuraminidase (NA)!!! ***
Measles (a Paramyxovirus)
To reduce mortality and complications you can give what vitamin?
AKA: Rubeola, 1st disease
Paranormal Mixer
Vitamin A
can reduce mortality and complications
Measles & Mumps (Paramyxovirus family)
Vaccine
Measles AKA: Rubeola, 1st disease
Paranormal Mixer
- MMR vaccine!
- Live attenuated vaccine to induce humoral and cell mediated immunity.
- Do NOT give to pregnant women.
- HIV pt should only get the vaccine if CD4 count is > 200.
Mumps (a Paramyxovirus)
signs and symptoms
Paranormal Mixer
- Fever, muscle pain, headache, and feeling tired.
- Usually followed by painful swelling of one or both parotid* salivary glands.
- Orchitis* (inflammation of testicle tissue) unilaterally (more rarely bilaterally) → can lead to impaired fertility and testicular atrophy.
- Meningitis*
* (Mumps replicates in the parotid glands, testes, and CNS)
Mumps (a Paramyxovirus)
VF
Paranormal Mixer
- Hemagglutinin (HA)
- Fusion proteins
- Neuraminidase (NA)
Respiratory Syncytial Virus (RSV) (a Paramyxovirus)
signs and symptoms
Paranormal Mixer
- Attaches to G protein to infect respiratory epithelial cells
- Bronchiolitis and Pneumonia (most common cause of these in infants!!!)
- Rhinitis and Pharyngitis
Respiratory Syncytial Virus (RSV) (a Paramyxovirus)
VF
Paranormal Mixer
- Fusion proteins (NO HA or NA for RSV)
Fusion proteins on the surface of the virus cause the cell membranes on nearby giant multinucleated cells to merge and stick together, forming syncytia.
Respiratory Syncytial Virus (RSV) (a Paramyxovirus)
Treatment
Paranormal Mixer
- Ribavirion for adults.*
* (Not children or pregnant women!!!)
- Palivisumab, a monoclonal antibody (IgG**) against the F protein of RSV, is used for high risk children and premies.
Parainfluenza (a Paramyxovirus)
signs and symptoms
Paranormal Mixer
Croup!
- AKA seal bark cough, inspiratory strider, or Laryngotracheobronchitis.
- characterized by a “barking” cough, stridor(harsh or grating sound), hoarseness, and difficulty breathing which usually worsens at night.
- Steeple radiographic sign on xray due to narrowing of the subglottic region from swelling.
Parainfluenza (a Paramyxovirus)
VF
Paranormal Mixer
Mainly affects children!!!
(Adults usually get a severe “cold”)
- Hemagglutinin (HA)
- Fusion proteins
- Neuraminidase (NA)
Rabies (a Rhabdovirus)
lab tests
Rabid Wrecking Yard
Bullet** shaped **NEG** sense _S_S RNA**
Enveloped virus
Helical nucleocapsid (like Filo and Arena)
Negri bodies (eosinophilic cytoplasmic inclusions) found in hippocampus (pyramidal cells) or cerebellum (soma of perkinje cells) on biopsy or autopsy.
Rabies (a Rhabdovirus)
Source
Rabid Wrecking Yard
Zoonotic virus
(carried by animals and transmitted to humans)
In U.S. most common carrier is bats
In undeveloped countries dogs also common carriers.
Squirrels, skunks, foxes, and raccoons also carry.
Rabies (a Rhabdovirus)
MOA
Rabid Wrecking Yard
- Glycoprotein on Rabies virus (G-protein) binds to Nicotinic ACh receptors in the post synaptic membrane in the NMJ.
- Replicates in the motor neurons motor end plates.
- Rabies moves retrograde via peripheral nerves (1-3 mm per day) to the dorsal root ganglia (can cause muscle spasms and tingling).
- Spreads to brain.
Rabies (a Rhabdovirus)
signs and symptoms
Rabid Wrecking Yard
- Muscle spasms and tingling
- ↑ salivary production (once virus is in the salivary glands) & excruciating spasms of muscles in throat and larynx → difficulty in swallowing (dysphagia) → foaming of mouth
- Encephalopathy and high fever
Rabies (a Rhabdovirus)
Vaccine / Antidote
Rabid Wrecking Yard
- Antidote w/ passive preformed antibodies (Human rabies IgG) **prior to symptoms (can be weeks to months before symptoms appear) AND…**
- Killed vaccine* for active immunity.
* (Killed vaccine tx is given even if just wake up with a bat in the room) *
Filovirus Family
lab tests
Soccer Field’o Virus
*** Marburg and Ebola ***
NEG** sense _S_S RNA**
Enveloped virus
Helical nucleocapsid (like Rabdo and Arena)
Filovirus Family
Viruses in the Filo family
and their source
Soccer Field’o Virus
- Marburg (usually bat* vector)
- Ebola (usually monkey* vector)
In the U.S. body fluids (especially after death) can spread Filovirus, so healthcare workers are most likely to get it.
* Either bats or monkeys can be vectors for both, and bats “might” be the viral reservoir.
Filovirus Family
signs and symptoms
Soccer Field’o Virus
*** Marburg and Ebola ***
- Hemorrhagic fever (sweating, fever, petechial rash)
- End organ failure
- Severe blood loss → Shock
- Death
Bunyavirus Family
lab tests
Paul Bunyavirus
NEG** sense _S_S RNA**
Enveloped virus (obtained from golgi bodies of host cells!!!)
3 Circular Segments (B.O.A.R. mnemonic)
Bunyavirus Family
Viruses in the Filo family
and their source
Paul Bunyavirus
1) Robovirus: transmitted through rodents (Deer mouse urine and pellets). (Robovirus like Arenavirus!)
* Hantavirus
2) Arboviruses:* transmitted through mosquito vector. (Arbovirus like the togavirus!)
* Rift Valley Fever, California Encephalitis (aedes mosquito)
* All Bunyaviruses except Hantavirus are Arboviruses.
Hantavirus (a Bunyavirus)
signs and symptoms
Paul Bunyavirus
- Causes pulmonary edema via capillary leak and prerenal azotemia (excess of nitrogen compounds in blood stream due to lack of blood flow to each kidney)
- Hemorrhagic fever
Rift Valley Fever AND California Encephalitis (Bunyaviruses)
signs and symptoms
Paul Bunyavirus
- Occurs mostly in children
- Myalgias and fever
- Seizures
- Encephalitis
(Usually not fatal, mostly causes neurological problems.)
Arenavirus Family
lab tests
Welcome to the Arenavirus
- NEG** sense _S_S RNA**
- AMISENSE!!! can also encode POS sense
- Enveloped virus
- Segmented, but only 2 reassortable segments (B.O.A.R. mnemonic)
- Helical nucleocapsid (like Rabdo and Filo)
- Characteristic granular sandy outer capsid on EM
Lymphocytic choriomeningitis virus (an Arenavirus)
source
AKA LCMV
Welcome to the Arenavirus
Transmitted by rodents.
(Robovirus like Bunyavirus!)
The common house mouse (Mus musculus) is the primary host, but other rodents such as hamsters can transmit LCMV if they were infected by a mouse.
Lymphocytic choriomeningitis virus (an Arenavirus)
signs and symptoms
AKA LCMV
Welcome to the Arenavirus
Biphasic febrile illness
1) Initial phase, which may last as long as a week:
* Fever, malaise, lack of appetite, muscle aches, headache, nausea, and vomiting
2) Following a few days of recovery, a 2nd phase may occur:
- Aseptic meningitis, encephalitis, or meningoencephalitis.
- also can cause acute hydrocephalus
Lymphocytic choriomeningitis virus (an Arenavirus)
Treatment and Inactivation of LCM virus
AKA LCMV
Welcome to the Arenavirus
- Tx is supportive care for symptoms such as meningitis.
No chronic infection has been described in humans, and after the acute phase of illness, the virus is cleared from the body
- LCMV can be inactivated
By heating, low pH, irradiation, detergents etc.
Riovirus Family
lab tests
A Race on the Rio
- NEG** sense _D_S RNA**
- DS! DS! DS! (Only RNA DS in sketchy!)
- NAKED virus
- avg of 11 Segments, 9-12 (B.O.A.R. mnemonic)
Rotavirus (a Riovirus)
key facts
A Race on the Rio
- Fecal-oral transmission
- Toxin mediated (NSP4 enterotoxin) secretory diarrhea.
- NSP4 ↑ Cl- permeability → secretory diarrhea that is explosive and watery (like norovirus, think Rotavirus sounds like rotate propeller).
- Classic outbreaks are in winter!
- Children most at risk (infants, daycare, etc).
- #1 cause of severe diarrhea in young children!
Colorado Tick Virus (a Riovirus)
key facts
A Race on the Rio
- Colorado Tick Virus
- Symptoms include myalgia, fever, and vomiting.
- NO rash !!!
- ddx from Rocky Mountain Spotted Fever due to lack of a rash with Colorado Tick Virus.
Rotavirus (a Riovirus)
Treatment
A Race on the Rio
Supportive care and oral rehydration
Rotavirus (a Riovirus)
Vaccine
A Race on the Rio
- Live attenuated oral vaccine
- 1st dose given before 3 months of age due to:
- Decreased efficacy
- May increase risk of intussusception*
* (stimulation and enlargement of peyers patches → which then act as lead points for the intestine to telescope into itself → can cut off blood supply → and possible bowel perforation.
