RNA Viruses Flashcards
HIV - microbiology & characteristics
ssRNA, retrovirus, Diploid genome (2 molecules of DNA»_space; genetic diversity)
3 key genes:
1. env
* envelope
* gp120 protein»_space; attachment to CD4, CCR5 (macrophages infected early), CXCR4 (T-cells infected later)
* gp41»_space;mediates fusion/entry into the cell
-
gag
* main structural components of the virus
* p24 protein»_space; capsid protein
* p17 protein»_space; matrix protein
3. pol
* allows HIV to replicate using the host’s own machinery
* Reverse Transcriptase
* Integrase»_space; integrates newly synthesized DNA into the host’s DNA
* Protease
Encoded polypetide gp160 is cleaved to produce gp120 and gp41 products.
HIV: clinical course
3 methods of transmission:
* SI
* Blood contact
* Vertical Transmission
Stages
1. Acute flu-like illness»_space; rapid increase in viral load
2. Latency phase»_space; 6 months - 10 years after infection. Very slowly replicating inside CD4+ (helper) T-cells»_space; plateau in viral load
3. Moderate Immunocompromise»_space; infection of immune cells happens more rapidly. Fall in CD4+ counts (<500)
4. AIDS»_space; Body can no longer defend itself from most infections. Need 1 of 2: opportunistic illness & less than 200 CD4+ T-cells.
Dx
* anti-HIV antibodies
* p24 antigen (ELISA)
Rx
* HAART = gold standard»_space; 2 NRTIs + Integrase inhibitor OR Protease Inhibitor
Prophylaxis
* PREP
* PEP
Reovirus
Rotavirus
Family that causes gastroenteritis illnesses.
- (+)sense, dsRNA, 10-12 segmented genome
Reassortment
* Segmented genome allows for antigenic shift (faster viral evolution when 2 strains infect the same cell)
* lead to major shifts in phenotype»_space; pandemics
- exonuclease mediated degradation
Rotavirus
* fecal-oral route
* crowded settings
* gastroenteritis»_space; villous atrophy
Dx
* Test stool for viral antigen
* RT-PCR
Rx
* supported
Prophylaxis
* live attenuated vaccines
Picornavirus
“PERCH for the picornaviruses”
- (+) sense, ssRNA, replicate in cytoplasm, non-enveloped, linear genome, replicated in cytoplasm
Polypeptide cleavage
* must be cleaved by viral proteases into the individual functional viral proteins
Key
1. Poliovirus
2. Echovirus
3. Rhinovirus
4. Coxsackievirus
5. Hepatitis A virus
Poliovirus
Picornavirus family
Presentation:
* Damages anterior horn = poliomyelitis (LMN disease)
Vaccination
* Live attenuated Vaccine (OPV) = “Sabin vaccine”
* stronger IgA response than inactivated (Salk)»_space; inhibits viral entry at gastric mucosa
* Rare VAPP
2nd vaccine
* Inactivated (Salk) vaccine
* no risk of causing VAPP»_space; only this is approved for use in developed countries
VAPP = vaccine-associated paralytic poliomyelitis
Echovirus
- Myocarditis
- Aseptic Meningitis
Picornavirus family
Presentation:
* Myocarditis»_space; chest pain & arrhythmias
* Aseptic meningitis»_space; fever, headache, nuchal rigidity (lumbar puncture)
Rhinovirus
Picornavirus family
- predominant cause of the common cold
- transmitted through respiratory droplets
- acid-labile»_space; destroyed by stomach acid, & cannot infect GI tract (like other Picornaviruses)
Presentation
* common cold»_space; coughing, sore throat, runny nose
Coxsackievirus
Picornavirus family
- Young children & infants
Presentation
Group A
* Aseptic meningitis
* Herpangina»_space; painful mouth blisters
* Hand, foot, & mouth disease
Group B
* heart inflammation»_space; myocarditis, pericarditis
* pleurodynia»_space; pain with each breath (viral infection of the lungs)
Hepatitis A Virus
Oysters & weird aversion to smoking.
Picornavirus family
- Seen in travelers & tourists outside the USA
- Fecal-oral route
- Shellfish +++ (oysters)»_space; Transmitted by ingesting undercooked/raw in the USA
Presentation
Acute hepatitis»_space;
* fever, jaundice, abdominal pain, elevated ALT/AST
* quite self-limited in nature
* does not lead to chronic hepatitis
* Aversion to smoking
Biopsy Dx - (same for all viral hepatitis types)
* Hepatic swelling & necrosis (“balloon degeneration”) due to ATP depletion and disruption of the cytoskeleton
* monocyte infiltration, hepatocyte necrosis
* Councilman bodies (round, pink eosinophilic apoptotic globules)
Other Dx
Acute infection
* Anti-HAV IgM
* PCR assay for viral RNA
Immunity
* Anti-HAV IgG
Prevention
* Inactivated (killed) vaccine
Hepatitis E Virus
Hepevirus – dangerous fulminant hepatitis in pregnancy.
Hepevirus family
- ssRNA, (+) sense, non-enveloped, linear chromosome
Hep E
* Fecal-oral transmission
* Acute hepatitis
* Fulminant (severe) hepatitis in pregnant women
Dx
* Liver biopsy»_space; hepatocyte swelling, monocyte infiltration, councilman bodies
* HEV-Ag (ELISA)
* HEV RNA by RT-PCR
* Anti-HEV antibodies may be seen in blood
Calicivirus family
Nora & Khaleesi !!
ssRNA, (+) sense, linear chromsome, non-eneveloped
Norovirus (Calicivirus family)
* Winter transmission (various modes)
* Gastroenteritis»_space; villous damage, diarrhea
Dx
* Mostly clinical
* Anti-norovirus IgM (serology)
Treatment
* Supportive care
* Self-resolving in 1-2 days
Khaleesi in the winter
Flavivirus family
HYD - SZ
- (+) sense, ssRNA, enveloped, linear chromosome
Key
1. Hepatitis C
2. Yellow Fever
3. Dengue
4. St. Louis & West Nile Virus
5. Zika
Hepatitis C Virus
Flavivirus family
Lack 3’ - 5’ exonuclease activity»_space; no proofreading ability
* antigenic variation of HCV envelope proteins (hypervariable region) due to frequent mutation
* host antibody production lags behind production of new mutant strains of HCV
Transmission
* Blood»_space; IV drug use, transfusion
Presentation
* Acute & chronic hepatitis
* Cirrhosis & HCC
Associated with:
* essential mixed cryoglobulinemia»_space; increase the viscosity of the blood
* ITP
* Autoimmune hemolytic anemia
Dx
Liver Biopsy
* Macrovesicular steatosis (fat vacuoles)
* hepatocyte ballooning degeneration
* monocyte infiltration
* councilman bodies
Rx
Ribavirin
* synthetic Guanosine analogue that inhibits RNA replication by directly binding to RNA polymerase
* inhibits IMP dehydrogenase»_space; depletes GTP needed for de novo purine synthesis
Weird blood things»_space;
Yellow Fever Virus
Yellow fever, Black vomit.
Flavivirus family
Transmission
* Aedes mosquitoes
Presentation
* High fever
* Black vomit»_space; hepatic dysfunction resulting in lack of vitamin K-dependent clotting factors»_space; bleeding in the GI tract
* Jaundice
* Hemorrhage
Liver biopsy - Dx
* Councilman bodies (eosinophilic apoptotic globules) on liver biopsy
Will see councilman bodies (on liver biopsy) in Yellow Fever Virus»_space; just like the hepatitis viruses.
Dengue Virus
Dengue breaks bones.
Flavivirus family
Transmission
* Aedes mosquitoes
Presentation
* Fever, nausea, headache
* Secondary infection with a different serotype can cause severe illness
* Bleeding»_space; blanching rash (petechiae, purpura)
* Hepatitis»_space; bump in AST/ALT, RUQ pain
* Bone break fever»_space; severe muscle & bone pain
* Retro-orbital pain
Dx
* Tourniquet test»_space; petechiae observed after a tourniquet is placed for 5 minutes
St. Louis Encephalitis / West Nile Virus
Flavivirus family
Transmission
* Aedes mosquitoes
Presentation
* Fever, cough, sore throat
* Meningoencephalitis
* Hyponatremia
* Flaccid paralysis
Dx
* PCR»_space; blood or CSF (lumbar puncture)
Zika Virus
Flavivirus family
Transmission
* Aedes mosquitoes
Presentation
* High fever, rash, arthralgia, conjunctivitis
* Teratogenic in utero
Dx
* RT-PCR
* Serology
Togavirus family
(+) sense, ssRNA, linear genome, enveloped, replicate in cytoplasm
Important Togaviruses:
Chikungunya
* Aedes mosquito»_space; co-infection with Dengue can occur
* Flu-like illness
* Polyarthralgias
* Diffuse macular rash
Eastern & Western Encephalitis
Rubella
Rubella
Togavirus family
Presentation
* Fever
* Lymphadenopathy»_space; postauricular or occipital
* Arthralgias
* Maculopapular rash»_space; spreads downward from the face (blanching petechiae)
* Congenital Rubella Syndrome»_space; SSNHL, cataracts, PDA, bluberry muffin rash (extramedullary hemaotpoiesis)
* Retro-orbital pain
Prophylaxis
* MMR vaccine»_space; live attenuated & given to babies between 12-15 months
* Live attenuated vaccines are contraindicated in severely immunocompromised patients
Rubella – eyes, ears, heart, skin.
Retrovirus family
ssRNA, (+) sense, linear chromosome, diploid genome, enveloped
- replicates in the nucleus (unlike most RNA viruses that replicate within the cytoplasm of infected cells)»_space; work by incorporating its genetic material into the host cell genome to replicate
- Possess a Reverse Transcriptase
Medical Importance
* HTLV = Adult T-Cell Leukemia/Lymphoma
* HIV/AIDS
Diploid RNA strands of Retroviruses allows for recombination to occur»_space;> increasing genetic diversity
Reverse Transcriptase
Uses RNA template to synthesize DNA. Crucial step in how HIV infects cells.
Coronavirus family
(+) sense, ssRNA, enveloped, linear chromosome, helical capsid
Presentation
* common cold, respiratory infections
SARS/MERS
* Pneumonia
Covid-19
* Transmission through respiratory droplets
* Incubation of 5-14 days
* Pneumonia
* Loss of smell/taste
Dx
* NAAT
* PCR
Rx
* Remdesivir in severe disease
* Steroids and ventilatory support for more severe cases
Orthomyoxvirus family
Influenza !!!
ssRNA, (-) sense, linear chromosome, enveloped, replicates in the nucleus (unlike other RNA viruses replicating in the cytoplasm), 8 segments, helical capsid
- Segments important for antigenic shift (reassortment)
Influenza virulence factors:
* Hemagglutinin (H)»_space; binds sialic acid receptors on the host cell to promote viral attachment/entry
* Neuraminidase (N)»_space;promotes progeny virion release (cleaves sialic acid)
Vaccines
* Create antibodies against Hemagglutinin
* IM injection»_space; killed
* Intranasal spray»_space; live-attenuated
Rx
* Oseltamavir»_space; inhibits NA, preventing viral invasion
* Amantadine»_space; impairs viral uncoating of Influenza A
- Needs to first be transcribed by RNA-dependent RNA polymerases.
- Anti-N antibodies only help to decrease the number of infected cells
Paramyxovirus family
ssRNA, (-) sense, linear chromosome, enveloped, replicates in the cytoplasm, non-segmented, helical capsid
4 major viral membrane antigens:
1. Hemagglutinin
2. F (fusion) protein
3. Matrix protein
4. Neuraminidase
RSV
Paramyxovirus family
Transmission
* Respiratory droplets
Presentation
* Bronchitis/bronchiolitis in babies
* Symptoms are worse in the winter
Dx
* RT-PCR
Rx - only for severe cases
* Palivizumab»_space; MAB targets F-protein of paramyxoviruses (stops fusion of viral envelope to epithelial cells)
* Ribavirin»_space; nuceloside antimetabolite
Parainfluenza Virus (Croup)
Paramyxovirus family
Transmission
* Respiratory droplets or fomite exposure
Presentation
* Croup»_space; barking “seal-like” cough and inspiratory stridor
* Severe»_space; pulsus paradoxus (secondary to upper airway obstruction)
Dx
* Steeple sign»_space; narrowing of upper trachea and subglottis, as seen on CXR
Rx
* supportive care
Measles
Paramyxovirus family
Transmission
* Respiratory droplets or contact
Presentation
* Fever
* 4 C’s»_space; cough, coryza (runny nose), conjunctivtis, coplik spots
* Coplik spots»_space; Red spots with blue-white center on the buccal mucosa
* Maculopapular rashes»_space; 1-2 days later. Starts on head and neck and spreads downward
* SSPE (encephalitis)»_space; late-stage complication of measles (years later)
Rx
* Vitamin A supplements
Prophylaxis
* MMR vaccine»_space; live-attenuated vaccine
Mumps
Paramyxovirus family
Transmission
* Respiratory droplets, direct contact, fomites
Presentation
* Non-specific prodrome
* Parotitis»_space; Swollen cheeks (parotid glands)
* Orchitis»_space; Swelling of the testicles – can lead to permanent infertility
* Pancreatitis»_space; GI symptoms with elevated amylase/lipase
* Aseptic meningitis
Rx
* Supportive
Prophylaxis
* MMR vaccine»_space; live-attenuated vaccine
Rhabdovirus family
Rabies
(-) sense, ssRNA, enveloped, linear genome, helical capsid
Rabies - characteristics
* **Bullet-shaped virus **(EM)
* Tranmission»_space; bat & raccoon bites
Rabies - pathophysiology
* Binds to **nicotinic ACh receptors **» migrates retrograde to CNS (via Dynein motors)
* Encephalitis»_space; hypersalivation, photophobia, hydrophobia, paralysis
Dx
Brain biopsy
* Negri bodies»_space; round eosinophilic cytoplasmic inclusions
RT-PCR
PEP
* Killed vaccine»_space; active immunization
* Rabies Ig»_space; passive immunization
Filovirus family
Ebola & Marburg Virus
(-) sense, ssRNA, enveloped, linear genome, helical capsid
Ebolaviruses
* bodily fluids and fomite contact
* High yield specific symptom»_space; hemorrhage
* **Hemorrhagic Shock **» DIC (primary cause of death in people with Ebola)
Marburg Hemorrhagic Viruses
* Weakened blood vessels and decreased blood clotting
Dx
* RT-PCR
Rx
* Supportive
Arenavirus family
- LCV
- Lassa Virus Encephalitis
(+/-) sense - BOTH, ssRNA, enveloped, circular genome, helical capsid, 2 segments
Lymphocytic choriomeningitis virus
* exposure from mice
* febrile aseptic meningoencephalitis
Lassa Fever Encephalitis
* Spread by rodents
* Rash with hemorrhage in eyes/nose/mouth
Dx
1. RT-PCR
2. ELISA
Rx
* Supportive
* Ribavirin
- Spread through rodents
- Ambisense (both positive and negative sense RNA)
- Segmented virus – antigenic shift
Bunyavirus family
Hantavirus
(-) sense, ssRNA, enveloped, circular genome, helical capsid, 3 segments
Transmission
* Arboviruses & anthropod-borne
Hantavirus
* rodents
* hemorrhagic fever
* pneumonia»_space; bilateral diffuse infiltrates
Dx
1. RT-PCR
2. ELISA
Deltavirus family
Hepatitis D Virus
(-) sense, ssRNA, enveloped, circular genome
Hepatitis D virus
* blood, sexual, perinatal transmission
* requires HBV co-infection»_space; cannot enter (needs HBV HBsAg) and replicate by itself
* Superinfection has worse prognosis than coinfection
hepatitis = liver inflammation
* HCC, cirrhosis
*
