RNA Viruses (+) Sense Flashcards

1
Q

List the (+) Sense RNA viruses? (9)

A
Poliovirus
Coxsackievirus
Rhinovirus
Hepatitis A
Calicivirus
Hepatitis C
Togavirus
Coronavirus
Retrovirus
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2
Q

What are the 3 main subgroups within the picornaviridae family?

A

Hepatitis A
Enteroviruses
Rhinoviruses

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3
Q

(+) Sense RNA replication

A

Viral RNA is already structured like mRNA so it just uses the host RNA Polymerase to get translated.

Viral RNA is “same sense” as host cell mRNA and can be directly translated by host cell RNA Polymerase.

All RNA (+) sense viruses replicate outside the nucleus - in the cytoplasm (Most viruses in general actually)

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4
Q

(-) Sense RNA replication

A

Virus must bring along its own RNA Polymerase

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5
Q

Picornaviridae RNA replication

A

Viral RNA is translated into a long polyprotein product, which when uncleaved cannot serve any function. The viruses have proteases that cleave the product into active viral subunits.

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6
Q

What viruses are included in the enteroviruses?

A

Subgroup of picornaviridae

Poliovirus
Coxsackie A and B
Echovirus

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7
Q

What is the number 1 cause of aseptic meningitis?

A

enteroviruses!

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8
Q

Describe the CSF findings for a viral (aseptic) meningitis?

A

CSF glucose normal
CSF shows no organisms (aseptic)
CSF has elevated protein

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9
Q

Picorniviridae family transmission

A

Most are fecal-oral (NOT rhinovirus tho)

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10
Q

What disease does poliovirus cause?

A

Polio…duh

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11
Q

What kind of virus is poliovirus?

A

It is an enterovirus and part of the picornavirus family

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12
Q

Where does poliovirus replicate?

A

It enters GI tract (ACID STABLE) and replicates in lymphoid tissue (tonsils, Peyer’s Patches)

Remember the Peyer’s Patches - 2-3 weeks

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13
Q

Where does poliovirus inflict its damage?

A

From lymphoid tissue, it spreads to anterior horn of lower motor neuron cell bodies

Causes paralysis 2-3 weeks after infection

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14
Q

Polio symptoms

A

Asymmetric flaccid paralysis (usually in lower legs)

Myalgias

Decreased DTRs

As paralysis ascends it can cause respiratory insufficiency (diaphragm paralysis) which is a big cause of death.

Can also cause aseptic meningitis

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15
Q

Polio Tx

A

No Tx

Can only avoid through prevention (2 kinds of vaccines)

1) Salk - inactivated (killed). Given parenterally through injection

It bypasses GI tract and only forms IgG. Not IgA (IgA is primary immunity in mucosal surfaces)

2) Sabin - live, attenuated given orally

Creates IgG and IgA but it may be shed in feces and revert to a form that can cause paralysis in someone else

USA uses killed vaccine.

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16
Q

Polio transmission

A

Fecal-oral (like most picornaviruses)

Usually in some parts of Asia/Africa

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17
Q

Coxsackie A

A

An enterovirus member of the picornavirus family

Hand, Foot and Mouth Disease

Red vesicular rash involving hands and feet (like syphilis and rickettsia rickettsii)

Aseptic meningitis

Often occurs during summer months

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18
Q

Coxsackie B

A

An enterovirus member of the picornavirus family

Dilated cardiomyopathy

Devil’s Grip - “Bornholm’s Disease” - pleurodynia

Extreme sharp pain in lower chest. Often unilateral. Makes it hard to breathe.

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19
Q

Coxsackie A and B Tx

A

Just supportive

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20
Q

Rhinovirus transmission

A

Inhalation (only picornavirus member that is not fecal-oral)

Also through fomites (like grubby hands)

It cannot go through GI tract - it is ACID LABILE

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21
Q

Coxsackie A and B transmission

A

Fecal-oral (like most picornaviruses)

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22
Q

How does Rhinovirus enter its host?

A

It attaches to ICAM-1 molecules

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23
Q

Why is it so hard to make a vaccine against rhinovirus?

A

It has 113 serotypes - almost impossible to cover them all

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24
Q

Where does rhinovirus grow best?

A

Upper respiratory tract - causes URI

Grows best at 33 C - slightly cooler than avg body temp

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25
Q

How is Hepatitis A transmitted?

A

Fecal-oral (Like most picornaviruses)

ACID STABLE

Hep A can be shed in feces and contaminate water supplies. In developed countries we purify drinking water to eliminate HepA (chlorine, bleach, UV, boil), but contaminated water is a common source of HepA in developing countries.

Hep A can be transmitted through shellfish that are caught in contaminated water sources, ESP if the shellfish are uncooked (common route in USA)

Hep A is commonly seen in travelers to endemic areas (esp in southern hemisphere)

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26
Q

How can you inactivate Hep A?

A

Chlorination
Bleach
UV irradiation
Boil (>85C for 1 min or more)

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27
Q

Hepatitis A presentation

A

Know that it’s caused by a picornavirus

Often clinically silent or subclinical

Can be anicteric (no jaundice)
Can also cause acute hepatitis though:

Fever, hepatomegaly, jaundice

So, Hep A leads to jaundice (esp in adults). Anicteric acute viral hepatitis in young children and infants.

Smokers with Hep A develop an aversion to smoking tobacco products.

One month duration of symptoms. Often self-limiting. No carrier state or chronic state.

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28
Q

Hep A prevention

A

Vaccine

Inactivated vaccine. Give to high risk patients (endemic areas, chronic liver disease, men who have sex with men)

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29
Q

Calicivirus RNA replication

A

It is a lot like the picornaviruses

Produces one long polyprotein that is cleaved by viral proteases

Does so in cytoplasm

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30
Q

What is the most common calicivirus?

A

Norovirus - “Norwalk virus”

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31
Q

Norovirus symptoms

A

viral gastoenteritis with explosive watery diarrhea

32
Q

Norovirus transmission

A

Know that it is a calicivirus

Outbreaks occur anywhere there are lots of people in close quarters - especially common on cruises (90% of all diarrhea illnesses on cruises)

Also strong association with outbreaks in day care centers and schools - children

Also through consumption of shellfish - esp handled/served raw. Really any situation where food is touched by people - like a buffet.

33
Q

What diseases are caused by Flaviviruses?

A

Dengue Fever
Yellow Fever
West Nile Virus
Hepatitis C

34
Q

Flavivirus general characteristic

A

Enveloped

Non-segmented (has only a single segment of RNA)

35
Q

Which diseases are transmitted through the Aedes Egyptei mosquito?

A
Dengue Fever (Flavivirus)
Yellow Fever (Flavivirus)
Rift Valley Fever (Bunyavirus)
California Encephalitis (Bunyavirus)
36
Q

Which disease is transmitted through the Culex mosquito?

A

West Nile Virus

37
Q

Dengue Fever presentation

A

From a Flavivirus

Mosquito vector (Aedes)

Infects bone marrow (also called break bone fever). There are 4 types of Dengue Fever, but Type 2 is the most important:

Causes thrombocytopenia (higher bleeding risk) and is a hemorrhagic fever.

Can lead to renal failure, septic shock or death

38
Q

Dengue Fever Tx

A

Mostly supportive

Keep well-hydrated

39
Q

Yellow Fever presentation

A

From a flavivirus

Mosquito vector (Aedes)

Causes jaundice, back ache, bloody diarrhea and bloody vomiting.

There is a live, attenuated vaccine for travelers.

40
Q

West Nile Virus presentation

A

From a flavivirus

Mosquito vector (Culex)

Birds are main reservoir.

Causes encephalitis.

Can cause myelitis leading to flaccid paralysis

Meningitis

Can lead to seizures and coma

41
Q

West Nile Virus Tx

A

Only supportive

42
Q

Hepatitis C transmission

A

A flavivirus

Through exposure to infected blood (blood transfusions) - Was a huge problem before 1990 - look out for a patient who received a blood transfusion before 1990 and has liver problems)

IV drug users who share needles

Through placenta, sex, breast feeding (Hep B is more likely through sex, but C is still possible)

43
Q

What is the leading cause of liver transplants?

A

Hepatitis C

44
Q

Hepatitis C vaccine

A

Not yet - It is more infectious than HIV so it would be nice

It is hard bc its envelope proteins vary their antigenic structure.

The virus-encoded RNA Polymerase does not have proof-reading exo-nuclease activity in the 3’ –> 5’ direction so RNA is prone to frequent mutations

Structure of protein also prone to frequent changes leading to high antigenic variation

45
Q

Hepatitis C clinical picture (general)

A

Causes hepatitis

Acute infection may lead to jaundice, RUQ pain, high liver enzymes, enlarged liver.

In Hep B most cases resolve after acute attach. Not here! 60-80% of acute infections of HepC become chronic.

In Hep C, lymphocytes will infiltrate the portal tract causing chronic inflammation that will lead to hepatocyte death.

Some pieces of liver might just succumb to fibrosis and cirrhosis.

Liver may also go into a frenzy to replace the cells. The reproducing cells may become malignant. Therefore, Hep C is a primary cause of hepatocellular carcinoma*

46
Q

Acute Hepatitis C

A

Hep C RNA will be present in serum during first 6 months. ALT will rise and fall by the end of 6 months.

In patients who manage to get over their initial infection, anti-HCV antibodies will arise within 2-3 months. The lag is due to new mutant strains being produced (antigenic variation)

Anti-HCV antibodies can exist in both acute and chronic infection since virus mutates so much.

Antibodies, even if present, soon become ineffective so there is no protection against recurring infection.

47
Q

Chronic Hepatitis C

A

Viral RNA persists in serum after 6 months. Liver biopsy will show a lot of lymphocytes in portal tract

Hep C is associated with cryoglobulins - serum proteins containing immunoglobulins (mostly IgM) that will precipitate out in cooler temperature.

48
Q

Hepatitis C Tx

A

Old way: Ribavirin + Interferon alpha

Other drugs can be used: Protease inhibitors or a Polymerase inhibitor like Sofosbuvir

Genotyping of virus must be done to determine what drugs to use.

49
Q

What viruses are classified as togaviruses?

A

Western Equine Encephalitis virus
Eastern Equine Encephalitis virus
Venezuelan Equine Encephalitis virus
Rubella*

50
Q

Which togaviruses are arboviruses and how are they treated?

A

Arborvirus is any virus that uses an arthropod vector

Here it is a mosquito

The equine encephalitis viruses are arboviruses.

Encephalitis presents with HA, Fever, Altered mental status, focal neuro deficits.

There is no Tx. Patients must protect themselves with netting, bug spray, protective clothing coverings

51
Q

Togavirus replication

A

One long polyprotein precursor that is cleaved by proteases

52
Q

What virus causes German Measles?

A

Rubella (a togavirus)

53
Q

What are the childhood exanthems?

A

Rubella (German Measles), Rubeola (Measles), Parvovirus B19 (Fifth Disease), HHV-6 (Roseola), Coxsackie A (Hand foot mouth), Strep pyogenes (Scarlett Fever), VZV (Chickenpox)

54
Q

What are the 3 different presentations of Rubella?

A

German measles

1) Congenital
2) Childhood
3) Adulthood

55
Q

Childhood Rubella presentation

A

Tender postauricular and occipital lymhadenopathy

Maculopapular rash - begins on face and spreads downward

Prodrome = Mild fever, lymphadenopathy, fatigue

Rash of Rubella moves faster than the rash of measles (Rubeola). It also does NOT darken or coalsce.

Rash is typically only present for 3 days

56
Q

Rubella transmission

A

Respiratory droplets

Or TORCH

57
Q

What are the TORCH infections?

A

infections that can spread mother - child through placenta

T = Toxoplasmosis
O = Other (Coxsackie, VZV, Chlamydia, HIV, Syphilis, Human T Lymphotropic Virus)
R = Rubella
C = CMV
H = HSV2 (neonatal herpes simplex)
58
Q

Congenital Rubella presentation

A

Main triad = congenital cataracts + sensorineural deafness + PDA

Other symptoms: (7)

Mental Retardation
Microcephaly 
Blindness
Jaundice
Pulmonic stenosis
Purpuric Blueberry Muffin Rash
Radiolucent bone lesions
59
Q

Adult Rubella presentation

A

Lymphadenopathy + fever

Also arthralgia and arthritis

60
Q

Rubella Tx

A

No Tx

Prevention: Vaccine

Covered by MMR vaccine: live attenuated

Includes humoral and cell-mediated immunity

Bc it’s live, do not give to pregnant women or immunocompromised patients. For HIV (+) patient, it is safe if CD4 > 200. Women should hold off on getting pregnant for at least 1 month if receiving vaccine.

61
Q

What patients are usually seen with Rubella?

A

Immigrants (not vaccinated)

62
Q

What does coronavirus look like?

A

Helical capsule/virus

63
Q

What disease does coronavirus cause?

A

SARS

MERS

also common cold sometimes

64
Q

SARS

A

disease caused by coronavirus

Acute bronchitis can lead to acute respiratory distress syndrome

Dx with test for antibodies or PCR. Absence of antibodies over 28 days is (-) finding

65
Q

SARS Tx

A

broad spectrum antibiotics

Ribavirin

Corticosteroids

66
Q

Retrovirus replication

A

HIV is a (+) RNA virus that gets converted to a DNA intermediate by an accompanying enzyme - reverse transcriptase

Once it becomes DNA it can get incorporated in host’s chromosomes and replicate forever

67
Q

What does HIV look like?

A

Retrovirus is a diploid RNA (+) virus - 2 molecules of (+) RNA in each virion

Cone - shaped capsule

68
Q

What are the 3 most important genes that HIV uses for its replication?

A

1) gag = p24. The capsule for RNA strands. It is cone-shaped.
2) env = responsible for making glycoproteins gp41 and gp120. These are proteins that serve to make the viral envelope. It also makes gp160 that gets cleaved to gp41 and gp120

gp41 = transmembrane protein
gp120 = outer glycoprotein. Will come in contact with host receptors

3) pol = reverse transcriptase

69
Q

HIV transmission

A

Mainly through sexual contact

Vertical (TORCH)

Through blood (IV drugs, needle sticks)

Immunocompromised***

70
Q

How does HIV infect its host?

A

HIV initially infects macrophages . It also targets CD4+ T cells (Helper T)

In order to enter the macrophages and T cells, there must be fusion of the virus with the host cell via receptors on the host cell - CCR5 and CXCR4 co-receptors.

Once virus binds these receptors, virus enters, uncoats, and utilizes reverse transcriptase to get incorporated into host’s DNA. It can then make new virions by using host machinery.

Gains entry via CCR5 receptors in early stages. CXCR4 in late stages.

71
Q

HIV clinical presentation

A

Prodrome (primary infection) consists of flu or mono-like symptoms with cervical lymphadenopathy.

Tonsils may have become enlarged too.
Fever
Lasts for several weeks and will get better on its own
CD4+ cells infected.

It remains latent for up to 10 years - virus is replicating in lymph nodes.

Steep decline in CD4+ cells

AIDS diagnosed when CD4+ 200 plus an AIDS-defining illness present

One such AIDS-defining illness directly caused by HIV is B-cell lymphoma called Diffuse Large B-Cell Lymphoma

72
Q

HIV testing

A

First, you need a screening test:

ELISA - looks for antibodies. If tested too early it may be a false (-). Multiple screenings up to 6 months after exposure should be done.

(+) ELISA requires a confirmatory test:

Western Blot - done on gel electrophoresis

Once diagnosed, get a viral load and CD4 count using PCR.

73
Q

How do you test for HIV in a neonate with an HIV(+) mother?

A

If you worried about vertical transmission:

ELISA or Western on a neonate would DEF be positive no matter what - mother has passed down antibodies to give neonate passive immunity.

Test neonate instead with HIV RNA and HIV DNA Nuclei Acid Amplification Test. This looks for the virus itself instead of the antibodies.

74
Q

HIV Tx

A

Antiretroviral therapy (HAART)

Combo therapy is always better than monotherapy since HIV is prone to mutations and the development of resistance.

1) NRTIs (Nucleoside Reverse Transcriptase Inhibitors) - This is the backbone of treatment. They pose as nucleotides, get incorporated into DNA by reverse transcriptase and then stop further elongation.

Use Zidovudine for pregnant patients - reduces risk of transmission by 2/3. Can start taking at 14 weeks all the way through 6 weeks post partem.

2) NNRTIs (Non-nucleoside Reverse Transcriptase Inhibitors) - Doesn’t incorporate itself.
3) Protease Inhibitors - inhibits the protease that cleaves proteins needs for viral replications
4) CCR5 inhibitors - virus can’t fuse with host cell

Maraviroc

There is a lot of HIV diversity so always genotype first to pick a good combo.

75
Q

Who receives HIV Tx?

A

Everyone! To prevent high viral load and low CD4

ESP for people with CD4