Viruses - RNA (+) sense Flashcards
POS sense RNA
shared replication MOA
POS sense RNA replication MOA
- Viral RNA structured like hosts mRNA
- POS sense RNA uses the hosts transcription factors! (since it’s the SAME SENSE as the host cell)
- It only needs hosts RNA polymerase (vs. NEG sense that brings its own RNA polymerase)
- ALL RNA POS (and most RNA NEG) replicate in the cytoplasm (where host cell RNA polymerase is located! makes sense!)
Picornavirus Family
lab tests
The Peak-orna Animal Nursery
POS sense SS RNA
Naked virus (No envelope!)
CSF findings of viral (aseptic) meningitis: Normal glucose, nothing (aseptic) when plated, and ↑ protein
Picornavirus Family
Viruses in the Picorna family
The Peak-orna Animal Nursery
- Hep A
- Enteroviruses (Polio, Cocksackie A & B, Echovirus)
- Rhinovirus*
All picornavirus are transmitted fecal-orally (acid-stable) except Rhinovirus which is transmitted respiratorily (acid-labile)
Picornavirus Family
Picornavirus RNA transmitted into
The Peak-orna Animal Nursery
Picornavirus RNA is tansmitted into:
A long protein product that contains viral proteases to cleave it into active viral subunits.
Poliovirus (a picornavirus)
Replication location and additioal MOA
(on top of the POS sense replication MOA)
The Flamingo Breeding Pool
- Poliovirus replicates in lymphoid tissue like tonsils and peyer’s patches found in the submucosa of the ilium.
- Replication occuring in the peyer’s patches takes 2-3 weeks.
- Infects the anterior horn of lower motor neuron (LMN) cell bodies causing paralysis (asymmetric)
Poliovirus (a picornavirus)
signs and symptoms
The Flamingo Breeding Pool
- Asymmetric paralysis concentrated in lower legs
- Myalgias
- ↓ Deep tendon reflexes
- Respiratory deficiency (due to paralysis of diaphragm)
- Aseptic meningitides
Poliovirus (a picornavirus)
2 Vaccines
The Flamingo Breeding Pool
1) Salk vaccine:
- Killed vaccine thats parenterally injected.
- Since it bypasses GI tract pts only form IgG antibodies (NOT IgA)
2) Sabin vaccine:
- _Live*_ and attenuated vaccine administered orally
- Makes IgA (in addition to IgG) since it goes through the stomach mucosa.
*Can be shed in feces and possibly cause paralysis in another person!
Poliovirus (a picornavirus)
Treatment
The Flamingo Breeding Pool
No tx available
Coxsackievirus (a picornavirus)
signs and symptoms of
Coxsackie A
Coxsackie Cockatoos
Coxsackie A is AKA “Hand, foot, and mouth disease”
- Red vesicular rash on palms* and fingers (hands), soles* (feet), and mouth (herpangina).
- Aseptic meningitis
- More common in summertime
* DX other hand/foot rashes, Syphilis and R. rickettsii
Coxsackievirus (a picornavirus)
signs and symptoms of
Coxsackie B
Coxsackie Cockatoos
Coxsackie A is AKA “Hand, foot, and mouth disease”
- Dilated cardiomyopathy
- “Devils grip“ (Bornholm’s disease): Extreme unilateral sharp pain in lower chest (Pleurodynia i.e. lung pain)
- Aseptic meningitis
- More common in summertime
Coxsackievirus (a picornavirus)
Treatment
Coxsackie Cockatoos
tx is supportive care
Rhinovirus (a picornavirus)
MOA
(on top of the POS sense replication MOA)
Rhino Petting Zoo (common cold*)
- Transmitted via inhalation (acid labile) or through fomites (like hands!!!).
- Attaches to I-CAM1 to enter host cells
- Needs to keep cool → grows best at 33°c → upper respiratory tract cooler due to movement of fresh air.
- 113 serotypes! So no vaccine!
*Rhinovirus and Coronavirus are the 2 major causes** of common **cold.
Hep A (a picornavirus)
source
Hungry Hungry Hep A hippos
- Transmitted fecal oral (Acid stable)
- Purification machines used to eliminate from contaminated water (Chlorine, Bleach, UV radiation, or Boil).
- In devoloping countries contaminated water** is often the source of infection, while in **developed areas its often contracted from shellfish pulled from poop contaminated water source.
Hep A (a picornavirus)
signs and symptoms
Hungry Hungry Hep A hippos
- Commonly is clinically silent w/out jaundice (Anicteric), but can also cause acute viral hep.
- Signs of acute viral hep include:
- Jaundice* (aka Icteric; Jaundice more often seen in adults, children less likely to have jaundice.), vomiting, and smoking aversion (in former smokers who get hep A)
- One month duration, self-_limiting_, _NO_ carrier state OR chronic state!
Hep A (a picornavirus)
Vaccine
Hungry Hungry Hep A hippos
Inactivated vaccine.
Calicivirus
replication MOA
Cali Sea Cruise
Naked POS** sense _R_NA**
Calici produces one long single protein that is cleaved by viral proteases into smaller active constituents. (like Picornaviruses!!!)
Replicates in the cytoplasm like all POS sense RNA.
Calicivirus
signs and symptoms
Cali Sea Cruise
- Most common strain of Calicivirus is NOROVIRUS (Norwalk virus)
- Calici is commonly acquired by people in closed quarters like cruises (90% of all diarrhea outbreaks on cruises!) and day care.
- Also acquired from shellfish or places where food is touched by people (buffets!)
- Explosive diarrhea!!!
Flavivirus Family
lab tests
Flavor Packed Flavi
POS sense SS RNA
Enveloped virus
Only a single segment* of RNA
* (non-segmented RNA; unlike Picorna or Calici which segment)
Flavivirus Family
Viruses in the Flavi family
Flavor Packed Flavi
- Hep C
- Dengue fever (“Breakbone fever”)
- Yellow fever
- West Nile virus
Flavivirus Family
Dengue fever (“Breakbone fever”)
Flavor Packed Flavi
- Humans are the reservoir
- Vector is the Aedes egyptei mosquito
- Infects bone marrow (type 2 Dengue; 4-5 types
- ↓ platlets → thrombocytopenia → ↑ risk of bleeding and hemorrhagic fever
- renal failure is common
- Septic shock and even death.
- Tx is supportive care with lots of fluids.
Flavivirus Family
Yellow fever
Flavor Packed Flavi
- Monkeys are the reservoir
- Vector is the Aedes egyptei mosquito
- SIgns and symptoms include jaundice (icteric), a back ache, bloody stool and diarrhea, and possible vomiting.
- Live attenuated vaccine
Flavivirus Family
West Nile virus
Flavor Packed Flavi
- Birds are the reservoir
- Vector is the mosquito’s
- SIgns and symptoms include encephalitis (major complication), meningitis, flaccid paralysis (from myelitis), coma, and seizures.
- Tx is supportive care
Hepatitis C (a flavivirus)
lab tests
The Hep Sea
- Enveloped, single segment (non-segmented) POS** sense _S_S RNA** (Like all flavivirus!)
- For acute Hep C infections: RNA in serum for first 6 months, ALT ↑ up to 10x normal levels before falling to a level still ↑ normal.
- Cryoglobulins that precipitate out at colder temps and contain 5 sided like IgM**
- Liver biospy will show lymphocytes in portal tract for chronic HCV
- If recover from initial Hep C inf → anti-HCV will ↑ after a few months (anti-HCV also seen in chronic Hep C).
Hepatitis C (a flavivirus)
source
The Hep Sea
- Exposure to infected blood
- Blood transfusions in 70’s -90’s
- IV drug use
- Placental, sex*, and breast feeding
* (Hep B more likely through sex, but Hep C still possible)
Hepatitis C (a flavivirus)
VF
The Hep Sea
- Variation of antigenic structure on the envelope proteins.
- Viron coated exonuclease lacks proofreading capacity in the 3’-5’ direction so the RNA is prone to frequent mutations.
Hepatitis C (a flavivirus)
Acute stage HCV
The Hep Sea
- Jaundice
- RUQ pain
- Inflammation of the liver
- Enlarged liver
- ↑ liver enzymes
Hepatitis C (a flavivirus)
Chronic stage HCV
The Hep Sea
60-80% of HCV pt’s become chronic! (Chronic if viral RNA present after 6 months!)
- Lymphocytes infiltrate portal tract → kiling hepatocytes → leading to fibrosis and cirrhosis.
- Liver can go into a frenzy and become malignant → hepatocellular carcinoma.
Hepatitis C (a flavivirus)
treatment
The Hep Sea
- Older tx:
Ribavirin w/ Interferon Alpha
- Newer tx (use polymerase / protease inhibitors):
Sofosbuvir (polymerase inhibitor)
Togavirus Family
replication MOA
Toga-Toga-Togavirus
Enveloped POS sense SS RNA
Toga produces one long single protein that is cleaved by viral proteases into smaller active constituents. (like Picornaviruses!!!)
Replicates in the cytoplasm like all POS sense RNA.
Togavirus Family
Viruses in the Toga family
Toga-Toga-Togavirus
1) 3 types of Arboviruses (Arthropod borne virus, Mosquitos vector)
Western equine encephalitis, Eastern equine encephalitis, Venezuelan equine encephalitis.
2) Rubella *** (Big buzzword = Immigrant) ***
AKA German measles, 3 day measles, or 3rd Disease
Rubella (a togavirus)
3 presentations of Rubella
AKA: German measles, 3 day measles, 3rd disease
Toga-Toga-Togavirus
- Congenital (TORCHeS infection!)
- Childhood
- Adult
Rubella (a togavirus)
Congenital presentations of Rubella
AKA: German measles, 3 day measles, 3rd disease
Toga-Toga-Togavirus
* TORCHeS infection!
- Classic traid of Congenital cataracts, Sensory-neural Deafness, PDA,
- Blueberry muffin rash* (purpric)
- Microcephaly, mental retardation
- Pulmonary stenosis, jaundice.
- Radiolucent bone lesions.
* Blueberry muffin rash also seen in CMV
Rubella (a togavirus)
Childhood presentations of Rubella
AKA: German measles, 3 day measles, 3rd disease
Toga-Toga-Togavirus
- Tender post-auricle** and **occipital lymphadenopathy
- Distinct maculopapular rash that starts on face and spreads downward, moves faster then measles, lasts 3 days, and does NOT darken or coalesce
- Respiratory drop transmission
- Prodrom of Rubella: mild fever, lymphadenopathy, fatigue
Rubella (a togavirus)
Adult presentations of Rubella
AKA: German measles, 3 day measles, 3rd disease
Toga-Toga-Togavirus
- Lymphadenopathy
- Seizures
- Knee pain, arthritis, and arthralgia
- Respiratory drop transmission
- Prodrom of Rubella: mild fever, lymphadenopathy, fatigue
Rubella (a togavirus)
Vaccine
AKA: German measles, 3 day measles, 3rd disease
Toga-Toga-Togavirus
- 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.
Togavirus Family
treatment
Toga-Toga-Togavirus
NO tx!
Coronavirus Family
lab tests
Kingdom of SARS
Encapsulated** helical _POS_ sense _S_S RNA**
Test for antibodies to SARS (or other strain) or PCR to confirm. (-) finding if absence of antibodies after 28 days.
Coronavirus Family
signs and symptoms
Kingdom of SARS
- Cause of common cold! (along with Rhinovirus!)
- Severe Acute Respiratory Syndrome (SARS)
- Middle East Respiratory Syndrome (MERS)
- Acute bronchitis → can lead to Acute Respiratory Distress Syndrom (ARDS, wet lung)
HIV (A Retrovirus)
Viral structure
One Cane to rule them all
- Enveloped POS sense SS RNA → DS DNA
- Diploid nature** (**2 molecules of RNA in each viron!)
HIV (A Retrovirus)
lab tests
for children / adults
(non neonates)
One Cane to rule them all
- SCREEN for antibodies with ELIZA test (repeat screen throughout 6 months; takes time to make antibodies)
- CONFIRM with Western Blot
- Measure viral LOAD and CD4 using PCB
- HIV → AIDs when CD4 < 200 OR CD4 > 200 w/ an AIDS defining illness
HIV (A Retrovirus)
lab tests
for neonates
One Cane to rule them all
- Use HIV RNA or HIV DNA amplification tests !!!
*** ELIZA and Western blot will always test (+) if mother has HIV or AIDS. They can give false (+) due to antibodies in the neonate that were passed on by the mother (giving the neonate passive immunity until it can make its own antibodies) ***
HIV (A Retrovirus)
replication MOA
One Cane to rule them all
- Binds: Attaches to the macrophage T-Cells via CCr5 (early stages) and CXCr4 (late stages) co-receptors
- Enters the macrophage
- Uncoats
- Replication: undergoes reverse transcription (forms DS DNA intermediate “provirus”) → migrates to nucleus → gets incorporated into hosts chromosomes → hosts genome now transcribes and translates new viral proteins
- Assembly: retrovirus capsids formed in hosts cell
- Egress: envelope proteins of retroviruses are acquired by budding from the plasma membrane (cell surface) of the host
- Maturation: Gag** and **Pol proteins of the retrovirus are cleaved by the retroviral protease → forming the mature and infectious form of the virus
HIV (A Retrovirus)
3 important genes
One Cane to rule them all
- Gag (p24): is a cone shaped capsule for the RNA strands
- Env protein (codes for gp41 and 120): 41 is transmembrane protein and 120 is outer protein. (to help remember think 420, it’s 41+120 without the 1’s)
- Pol: reverse transcriptase
HIV (A Retrovirus)
Source
One Cane to rule them all
Transmitted primarily through:
- Sex
- Blood transfusions
- Verticle transmission (* TORCHeS infection! *)
HIV (A Retrovirus)
signs and symptoms
One Cane to rule them all
- Prodromal like flu (or mono-like) with cervical lymphadenopathy, tonsils may be enlarged, fever
- May last for several weeks → Gets better on its own → But CD4 (+) cells are infected
- HIV latent for 10 years → Replicating in lymph nodes → CD4 drops < 200 → progresses to AIDS
- AIDS ↑ risk of B cell lymphoma, diffuse large B cell lymphoma
HIV (A Retrovirus)
treatments
One Cane to rule them all
Highly Active Antiretroviral Therapy (HAART) anti-HIV “cocktail” — is a combination of three or more drugs.
- Nucleoside Reverse Transcriptase Inhibitors (NRTI) are the backbone of HAART therapy.
- Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)
- Protease Inhibitors (PI)
- Fusion Inhibitors
HIV (A Retrovirus)
NRTI treatments MOA
One Cane to rule them all
Nucleoside Reverse Transcriptase Inhibitors (NRTI) are nucleoside analogs that contain faulty versions of the building blocks (nucleotides) used by reverse transcriptase to convert RNA to DNA, halting prolonation.
HIV (A Retrovirus)
NNRTI treatments MOA
One Cane to rule them all
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) binds to and block HIV reverse transcriptase.
HIV (A Retrovirus)
PI treatments MOA
One Cane to rule them all
Protease Inhibitors (PI) prevent cleavage of proteins for viral replication.
HIV (A Retrovirus)
Fusion Inhibitor treatments MOA
One Cane to rule them all
Fusion Inhibitors act against HIV by preventing the virus from fusing with the inside of a cell, preventing it from replicating.
- example is Miravoroc which is a CCr5 inhibitor
HIV (A Retrovirus)
treatments pre/post pregnancy
One Cane to rule them all
The NRTI Zidovudine is best for pregnant women, during labor, and post partum pts.
It can reduce the risk of transmision to the baby by 2/3 if taken from 14 weeks of gestation to 6 weeks post partum.
