3 methods of transmission: SI Blood contact Vertical Transmission Stages 1. Acute flu-like illness >> rapid increase in viral load 2. Latency phase >> 6 months - 10 years after infection. Very slowly replicating inside CD4+ (helper) T-cells >> plateau in viral load 3. Moderate Immunocompromise >> infection of immune cells happens more rapidly. Fall in CD4+ counts ( > 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 >> 2 NRTIs + Integrase inhibitor OR Protease Inhibitor Prophylaxis PREP PEP

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 >> pandemics exonuclease mediated degradation Rotavirus fecal-oral route crowded settings gastroenteritis >> villous atrophy Dx Test stool for viral antigen RT-PCR Rx supported Prophylaxis live attenuated vaccines

Picornavirus family Presentation: Damages anterior horn = poliomyelitis (LMN disease) Vaccination Live attenuated Vaccine (OPV) = "Sabin vaccine" stronger IgA response than inactivated (Salk) >> inhibits viral entry at gastric mucosa Rare VAPP 2nd vaccine Inactivated (Salk) vaccine no risk of causing VAPP >> only this is approved for use in developed countries VAPP = vaccine-associated paralytic poliomyelitis

Echovirus 1. Myocarditis 2. Aseptic Meningitis

Picornavirus family Presentation: Myocarditis >> chest pain & arrhythmias Aseptic meningitis >> fever, headache, nuchal rigidity (lumbar puncture)

Picornavirus family predominant cause of the common cold transmitted through respiratory droplets acid-labile >> destroyed by stomach acid, & cannot infect GI tract (like other Picornaviruses) Presentation common cold >> coughing, sore throat, runny nose

Flavivirus family Lack 3' - 5' exonuclease activity >> 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 >> IV drug use, transfusion Presentation Acute & chronic hepatitis Cirrhosis & HCC Associated with: essential mixed cryoglobulinemia >> 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 >> depletes GTP needed for de novo purine synthesis Weird blood things >>

RNA Viruses Flashcards by Henna Tiwary

HIV - microbiology & characteristics

ssRNA, retrovirus, Diploid genome (2 molecules of DNA&raquo_space; genetic diversity)

3 key genes:

1. env
* envelope
* gp120 protein&raquo_space; attachment to CD4, CCR5 (macrophages infected early), CXCR4 (T-cells infected later)
* gp41&raquo_space;mediates fusion/entry into the cell

gag
* main structural components of the virus
* p24 protein&raquo_space; capsid protein
* p17 protein&raquo_space; matrix protein

3. pol
* allows HIV to replicate using the host’s own machinery
* Reverse Transcriptase
* Integrase&raquo_space; integrates newly synthesized DNA into the host’s DNA
* Protease

Encoded polypetide gp160 is cleaved to produce gp120 and gp41 products.

How well did you know this?

Not at all

Perfectly

HIV: clinical course

3 methods of transmission:
* SI
* Blood contact
* Vertical Transmission

Stages
1. Acute flu-like illness&raquo_space; rapid increase in viral load
2. Latency phase&raquo_space; 6 months - 10 years after infection. Very slowly replicating inside CD4+ (helper) T-cells&raquo_space; plateau in viral load
3. Moderate Immunocompromise&raquo_space; infection of immune cells happens more rapidly. Fall in CD4+ counts (<500)
4. AIDS&raquo_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&raquo_space; 2 NRTIs + Integrase inhibitor OR Protease Inhibitor

Prophylaxis
* PREP
* PEP

How well did you know this?

Not at all

Perfectly

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&raquo_space; pandemics

exonuclease mediated degradation

Rotavirus
* fecal-oral route
* crowded settings
* gastroenteritis&raquo_space; villous atrophy

Dx
* Test stool for viral antigen
* RT-PCR

Rx
* supported

Prophylaxis
* live attenuated vaccines

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Poliovirus

Picornavirus family

Presentation:
* Damages anterior horn = poliomyelitis (LMN disease)

Vaccination
* Live attenuated Vaccine (OPV) = “Sabin vaccine”
* stronger IgA response than inactivated (Salk)&raquo_space; inhibits viral entry at gastric mucosa
* Rare VAPP

2nd vaccine
* Inactivated (Salk) vaccine
* no risk of causing VAPP&raquo_space; only this is approved for use in developed countries

VAPP = vaccine-associated paralytic poliomyelitis

How well did you know this?

Not at all

Perfectly

Echovirus

Myocarditis
Aseptic Meningitis

Picornavirus family

Presentation:
* Myocarditis&raquo_space; chest pain & arrhythmias
* Aseptic meningitis&raquo_space; fever, headache, nuchal rigidity (lumbar puncture)

How well did you know this?

Not at all

Perfectly

Rhinovirus

Picornavirus family

predominant cause of the common cold
transmitted through respiratory droplets
acid-labile&raquo_space; destroyed by stomach acid, & cannot infect GI tract (like other Picornaviruses)

Presentation
* common cold&raquo_space; coughing, sore throat, runny nose

How well did you know this?

Not at all

Perfectly

Coxsackievirus

Picornavirus family

Young children & infants

Presentation
Group A
* Aseptic meningitis
* Herpangina&raquo_space; painful mouth blisters
* Hand, foot, & mouth disease

Group B
* heart inflammation&raquo_space; myocarditis, pericarditis
* pleurodynia&raquo_space; pain with each breath (viral infection of the lungs)

How well did you know this?

Not at all

Perfectly

Hepatitis A Virus

Oysters & weird aversion to smoking.

Picornavirus family

Seen in travelers & tourists outside the USA
Fecal-oral route
Shellfish +++ (oysters)&raquo_space; Transmitted by ingesting undercooked/raw in the USA

Presentation
Acute hepatitis&raquo_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

How well did you know this?

Not at all

Perfectly

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&raquo_space; hepatocyte swelling, monocyte infiltration, councilman bodies
* HEV-Ag (ELISA)
* HEV RNA by RT-PCR
* Anti-HEV antibodies may be seen in blood

How well did you know this?

Not at all

Perfectly

Calicivirus family

Nora & Khaleesi !!

ssRNA, (+) sense, linear chromsome, non-eneveloped

Norovirus (Calicivirus family)
* Winter transmission (various modes)
* Gastroenteritis&raquo_space; villous damage, diarrhea

Dx
* Mostly clinical
* Anti-norovirus IgM (serology)

Treatment
* Supportive care
* Self-resolving in 1-2 days

Khaleesi in the winter

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Hepatitis C Virus

Flavivirus family

Lack 3’ - 5’ exonuclease activity&raquo_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&raquo_space; IV drug use, transfusion

Presentation
* Acute & chronic hepatitis
* Cirrhosis & HCC

Associated with:
* essential mixed cryoglobulinemia&raquo_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&raquo_space; depletes GTP needed for de novo purine synthesis

Weird blood things&raquo_space;

How well did you know this?

Not at all

Perfectly

Yellow Fever Virus

Yellow fever, Black vomit.

Flavivirus family

Transmission
* Aedes mosquitoes

Presentation
* High fever
* Black vomit&raquo_space; hepatic dysfunction resulting in lack of vitamin K-dependent clotting factors&raquo_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&raquo_space; just like the hepatitis viruses.

How well did you know this?

Not at all

Perfectly

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&raquo_space; blanching rash (petechiae, purpura)
* Hepatitis&raquo_space; bump in AST/ALT, RUQ pain
* Bone break fever&raquo_space; severe muscle & bone pain
* Retro-orbital pain

Dx
* Tourniquet test&raquo_space; petechiae observed after a tourniquet is placed for 5 minutes

How well did you know this?

Not at all

Perfectly

St. Louis Encephalitis / West Nile Virus

Flavivirus family

Transmission
* Aedes mosquitoes

Presentation
* Fever, cough, sore throat
* Meningoencephalitis
* Hyponatremia
* Flaccid paralysis

Dx
* PCR&raquo_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&raquo_space; co-infection with Dengue can occur
* Flu-like illness
* Polyarthralgias
* Diffuse macular rash

Eastern & Western Encephalitis

Rubella

Rubella

Togavirus family

Presentation
* Fever
* Lymphadenopathy&raquo_space; postauricular or occipital
* Arthralgias
* Maculopapular rash&raquo_space; spreads downward from the face (blanching petechiae)
* Congenital Rubella Syndrome&raquo_space; SSNHL, cataracts, PDA, bluberry muffin rash (extramedullary hemaotpoiesis)
* Retro-orbital pain

Prophylaxis
* MMR vaccine&raquo_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)&raquo_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&raquo_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)&raquo_space; binds sialic acid receptors on the host cell to promote viral attachment/entry
* Neuraminidase (N)&raquo_space;promotes progeny virion release (cleaves sialic acid)

Vaccines
* Create antibodies against Hemagglutinin
* IM injection&raquo_space; killed
* Intranasal spray&raquo_space; live-attenuated

Rx
* Oseltamavir&raquo_space; inhibits NA, preventing viral invasion
* Amantadine&raquo_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** >> MAB targets **F-protein** of paramyxoviruses (stops fusion of viral envelope to epithelial cells) * **Ribavirin** >> nuceloside antimetabolite

Parainfluenza Virus (Croup)

**Paramyxovirus** family **Transmission** * Respiratory droplets or **fomite exposure** **Presentation** * **Croup** >> barking "seal-like" cough and inspiratory stridor * Severe >> **pulsus paradoxus** (secondary to upper airway obstruction) **Dx** * **Steeple sign** >> 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** >> cough, coryza (runny nose), conjunctivtis, coplik spots * **Coplik spots** >> Red spots with **blue-white center** on the buccal mucosa * **Maculopapular rashes** >> 1-2 days later. Starts on head and neck and **spreads downward** * **SSPE (encephalitis)** >> late-stage complication of measles (years later) **Rx** * Vitamin A supplements **Prophylaxis** * MMR vaccine >> live-attenuated vaccine

Mumps

**Paramyxovirus** family **Transmission** * Respiratory droplets, direct contact, fomites **Presentation** * Non-specific prodrome * **Parotitis** >> Swollen cheeks (parotid glands) * **Orchitis** >> Swelling of the testicles -- can lead to permanent infertility * **Pancreatitis** >> GI symptoms with elevated amylase/lipase * Aseptic meningitis **Rx** * Supportive **Prophylaxis** * MMR vaccine >> live-attenuated vaccine

**Rhabdovirus** family

**Rabies** **(-) sense**, ssRNA, **enveloped**, linear genome, **helical capsid** Rabies - characteristics * **Bullet-shaped virus **(EM) * Tranmission >> **bat** & **raccoon** bites Rabies - pathophysiology * Binds to **nicotinic ACh receptors **>> migrates **retrograde to CNS** (via Dynein motors) * **Encephalitis** >> hypersalivation, photophobia, hydrophobia, paralysis Dx **Brain biopsy** * Negri bodies >> round eosinophilic cytoplasmic inclusions **RT-PCR** **PEP** * **Killed vaccine** >> active immunization * **Rabies Ig** >> passive immunization

**Filovirus** family

Ebola & Marburg Virus **(-) sense**, ssRNA, **enveloped**, linear genome, **helical capsid** **Ebolaviruses** * bodily fluids and fomite contact * High yield specific symptom >> **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 ## Footnote * 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 >> 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** >> cannot enter (needs **HBV HBsAg**) and replicate by itself * Superinfection has worse prognosis than coinfection **hepatitis** = liver inflammation * HCC, cirrhosis *