Viruses - RNA (+) sense Flashcards
1
Q
POS sense RNA
shared replication MOA
A
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!)
2
Q
Picornavirus Family
lab tests
A
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
3
Q
Picornavirus Family
Viruses in the Picorna family
A
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)
4
Q
Picornavirus Family
Picornavirus RNA transmitted into
A
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.
5
Q
Poliovirus (a picornavirus)
Replication location and additioal MOA
(on top of the POS sense replication MOA)
A
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)
6
Q
Poliovirus (a picornavirus)
signs and symptoms
A
The Flamingo Breeding Pool
- Asymmetric paralysis concentrated in lower legs
- Myalgias
- ↓ Deep tendon reflexes
- Respiratory deficiency (due to paralysis of diaphragm)
- Aseptic meningitides
7
Q
Poliovirus (a picornavirus)
2 Vaccines
A
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!
8
Q
Poliovirus (a picornavirus)
Treatment
A
The Flamingo Breeding Pool
No tx available
9
Q
Coxsackievirus (a picornavirus)
signs and symptoms of
Coxsackie A
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
10
Q
Coxsackievirus (a picornavirus)
signs and symptoms of
Coxsackie B
A
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
11
Q
Coxsackievirus (a picornavirus)
Treatment
A
Coxsackie Cockatoos
tx is supportive care
12
Q
Rhinovirus (a picornavirus)
MOA
(on top of the POS sense replication MOA)
A
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.
13
Q
Hep A (a picornavirus)
source
A
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.
14
Q
Hep A (a picornavirus)
signs and symptoms
A
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!
15
Q
Hep A (a picornavirus)
Vaccine
A
Hungry Hungry Hep A hippos
Inactivated vaccine.
16
Q
Calicivirus
replication MOA
A
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.
17
Q
Calicivirus
signs and symptoms
A
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!!!
18
Q
Flavivirus Family
lab tests
A
Flavor Packed Flavi
POS sense SS RNA
Enveloped virus
Only a single segment* of RNA
* (non-segmented RNA; unlike Picorna or Calici which segment)
19
Q
Flavivirus Family
Viruses in the Flavi family
A
Flavor Packed Flavi
- Hep C
- Dengue fever (“Breakbone fever”)
- Yellow fever
- West Nile virus
20
Q
Flavivirus Family
Dengue fever (“Breakbone fever”)
A
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.
21
Q
Flavivirus Family
Yellow fever
A
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
22
Q
Flavivirus Family
West Nile virus
A
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
23
Q
Cirrhosis
lab tests
A
The Hep Sea
- ↑ ALT (Alanine aminotransferase from liver)
- ↑AST with AST>ALT (Aspartate aminotransferase from liver)
- ↑ ALP (Alkaline phosphatase from bile ducts)
- ↓ albumin
- normal or ↑ biliruben
- normal proteins (↓ albumin but ↑ in other proteins)
24
Q
Hepatitis C (a flavivirus)
lab tests
A
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).
25
**_Hepatitis C_** **(a **_flavi_**virus)**
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)
26
**_Hepatitis C_** **(a **_flavi_**virus)**
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**.
27
**_Hepatitis C_** **(a **_flavi_**virus)**
**Acute** stage **HCV**
**_The Hep Sea_**
* Jaundice
* RUQ pain
* Inflammation of the liver
* Enlarged liver
* ↑ liver enzymes
28
**_Hepatitis C_** **(a **_flavi_**virus)**
**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** → ****_hepato_**cellular _carcinoma_**.
29
**_Hepatitis C_** **(a **_flavi_**virus)**
treatment
**_The Hep Sea_**
* **_Older tx_:**
**Rib**avirin w/ **I**nterferon **Alpha**
* **_Newer tx (use polymerase / protease inhibitors)_:**
Sofosbuvir (polymerase inhibitor)
30
**_Togavirus Family_**
replication MOA
**_Toga-Toga-Togavirus_**
**_Enveloped_** **_POS_** sense ****_S_**S** ****_R_**NA**
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**.
31
**_Togavirus Family_**
Viruses in the Toga family
**_Toga-Toga-Togavirus_**
**1)** _**3** types of **Arbo**viruses_ (**_Ar_**thropod **_bo_**rne 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**
32
**_Rubella_** **(a **_toga_**virus)**
**3 presentations** of **_Rubella_**
**_AKA_****:** **German** measles, **3 day** measles, **3rd** disease
**_Toga-Toga-Togavirus_**
1. **Congenital** (**TO**_R_**CHeS** infection!)
2. **Childhood**
3. **Adult**
33
**_Rubella_ (a **_toga_**virus)**
**_Congenital_ presentations** of **_Rubella_**
**_AKA_****:** **German** measles, **3 day** measles, **3rd** disease
**_Toga-Toga-Togavirus_**
**\*** **TO**_R_**CHeS** 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**
34
**_Rubella_ (a **_toga_**virus)**
**_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**
35
**_Rubella_ (a **_toga_**virus)**
**_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**
36
**_Rubella_ (a **_toga_**virus)**
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_**.
37
**_Togavirus Family_**
treatment
**_Toga-Toga-Togavirus_**
## Footnote
**_NO_ tx!**
38
_**TORCHeS** Infections_
_**TORCHeS** Infections_:
**_T_**oxoplasmosis
**_O_**ther (HIV, VZV, Parvovirus B19, enteroviruses, others)
**_R_**ubella
**_C_**ytomegalovirus
**_He_**rpes
**_S_**yphilis
39
**_Coronavirus Family_**
lab tests
**_Kingdom of SARS_**
**En**_capsulated_** _helical_ _POS**_ sense _****S**_S **_R_**NA**
**Test for** **_antibodies_** to SARS (or other strain) **or _PCR_** to confirm. **(-) finding** **if absence** of **antibodies after 28 days**.
40
**_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**)
41
**_HIV_ (A **_Retro_**virus)**
Viral structure
**_One Cane to rule them all_**
* **_Enveloped_** **_POS_** sense ****_S_**S** ****_R_**NA → **_D_**S **_D_**NA**
* **_Diploid nature**_ (_**2_ molecules** of ****_R_**NA in each viron!**)
42
**_HIV_ (A **_Retro_**virus)**
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**
43
**_HIV_ (A **_Retro_**virus)**
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) **\*\*\***
44
**_HIV_ (A **_Retro_**virus)**
replication MOA
**_One Cane to rule them all_**
1. **_Binds_:** Attaches **to** the **_macrophage_** **_T-Cells_** via **_CCr5_** (**early** stages) and **_CXCr4_** (**late** stages) **co-receptors**
2. **_Enters_** the **macrophage**
3. **_Uncoats_**
4. **_Replication_:** undergoes **reverse transcription** (**forms **_D_**S **_D_**NA** intermediate "provirus") → **migrates to _nucleus_** → gets **incorporated into hosts chromosomes** → **_hosts genome_** now **transcribes** and **translates** new **viral proteins**
5. **_Assembly_:** retrovirus capsids formed in hosts cell
6. **_Egress_: envelope proteins** of retroviruses are **acquired by budding** from the plasma membrane (cell surface) of the host
7. **_Maturation_:** **_Gag**_ and _**Pol_ proteins** of the retrovirus are **cleaved by** the **_retroviral protease_** → forming the mature and infectious form of the virus
45
**_HIV_ (A **_Retro_**virus)**
3 important genes
**_One Cane to rule them all_**
1. **_Gag_ (_p24_):** is a **_cone_ shaped _capsule_** **for** the ****_R_**NA** strands
2. **_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)
3. **_Pol_: reverse** **transcriptase**
46
**_HIV_** **(A **_Retro_**virus)**
Source
**_One Cane to rule them all_**
_**Transmitted** primarily through_:
* **Sex**
* **Blood** transfusions
* **Verticle** transmission (**\* T**_O_**RCHeS infection! \*)**
47
**_HIV_** **(A **_Retro_**virus)**
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**
48
**_HIV_ (A **_Retro_**virus)**
treatments
**_One Cane to rule them all_**
Highly Active Antiretroviral Therapy (**HAART**) anti-HIV **"cocktail"** — is a combination of three or more drugs.
1. ****_N_**ucleoside **_R_**everse **_T_**ranscriptase **_I_**nhibitors** (**_NRTI_**) are the backbone of HAART therapy.
2. ****_N_**on-**_N_**ucleoside **_R_**everse **_T_**ranscriptase **_I_**nhibitors** (**_NNRTI_**)
3. ****_P_**rotease **_I_**nhibitors** (**_PI_**)
4. **Fusion Inhibitors**
49
**_HIV_ (A **_Retro_**virus)**
**_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**.
50
**_HIV_ (A **_Retro_**virus)**
**_NNRTI_** treatments **MOA**
**_One Cane to rule them all_**
**_Non-Nucleoside Reverse Transcriptase Inhibitors_** (**_NNRTI_**) **binds** to and **block** HIV **reverse transcriptase**.
51
**_HIV_ (A **_Retro_**virus)**
**_PI_** treatments **MOA**
**_One Cane to rule them all_**
**_Protease Inhibitors_** (**_PI_**) **prevent cleavage** of proteins for viral replication.
52
**_HIV_ (A **_Retro_**virus)**
**_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**
53
**_HIV_ (A **_Retro_**virus)**
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**.
