Viruses I - RNA and V. Hepatitis - KMS Flashcards
What mechanism do viruses have for energy production?
They don’t.
As obligate intracellular parasites, they pirate the resources of the host.
Will a single stranded, positive sense RNA virus need special viral proteins in order to infect the host cell once it gains entry? What viral enzyme must it synthesize to proliferate?
+RNA = positive reading frame
Viral genome in this case is much like host cell mRNA, and can start hijacking host transcription machinery immediately.
+RNA viruses must make an RNA-dependent RNA polymerase enzyme in order to make new copies of their genome and proliferate
Will a negative sense single stranded RNA virus need to have special viral enzymes in the viral particle in order to infect the host cell once it gains entry?
(-) RNA virus will need to be packaged with a viral RNA dependent RNA polymerase in order to make copies of its genome with the right reading frame - positive sense RNA copies. Once these copies are made, they can be fed into the host cell’s transcription machinery.
(Enzyme must be packaged into the virus, virus cannot establish infection or replicate until it makes RNA that can work with the host cell machinery.
Retroviruses have what kind of genetic material in the viral particle? What enzymes does this type need in order to infect a cell?
(diploid) positive sense RNA
Retroviruses will need to have reverse transcriptase enzyme packaged in the viral particle in order to make a DNA copy of its genome
Virus will also need integrase enzyme in order to insert the DNA copy of its genome into the host cell DNA
What viral families are non-enveloped? Which are enveloped?
Non-enveloped:
Picornaviruses
Caliciviruses
Reoviruses
Papovaviruses
Adenoviruses
Parvoviruses
Enveloped: everything else
What 4 viruses are associated with illness in the respiratory system?
Adenovirus
Rhinovirus
Influenze viruses A, B
Resp. Synctial Virus (RSV)
What 8 viruses are associated with infections of the digestive system?
Mumps virus
Rotavirus
Norovirus/Norwalk
Hepatitis A, B, C, D, and E
What 5 viruses are associated with systemic infections with skin eruptions?
Measles virus
Rubella virus
Varicella-Zoster virus (VZV)
Herpes Simplex virus 1 (HSV1)
Herpes Simplex virus 2 (HSV2)
What 3 viruses are associated with systemic infection with hematopoietic disorders?
Cytomegalovirus (CMV)
Epstein-Barre Virus (EBV)
HIV-1 and HIV-2
The Orthomyxovirus family causes what disease?
Influenza
Orthomyxoviruses have what kind of genetic material? Are they enveloped?
- ssRNA, enveloped
(will be packaged with a viral RNA-dependent RNA polymerase)
What determines the viral types of the Influenza genus?
Nucleoprotein antigen determines virus type A, B or C
What Influenza viral type can cause the most severe disease? Least severe?
A is most severe
B is middling
C is least severe
What Influenza viral type has an animal reservoir?
Type A
What are 2 important markers on the Influenza envelope? Why are these important?
2 surface glycoproteins:
(H) - hemagglutinin - mediates attachment to respiratory mucosa and RBCs
(N) - neuraminidase - mucus liquifaction leading to local viral spread
Changes in surface antigens/glycoproteins produce new strains of Influenza, and can lead to pandemics
What is the difference between antigenic drift versus antigenic shift in the case of Influenza?
Antigenic drift - mutations in RNA leading to minor changes in the antigenic character of H and N surface glycoproteins
- cause of yearly epidemics
Antigenic shift - rearrangement of genome segments leading to major changes in the antigenic character of the H and N molecules
What are some major flu pandemics that have happened? What were the surface glycoprotein variants, and year of outbreak?
(This card might not be high yield, more of a CYA)
1957 Asian flu H2N2
1968 Hong Kong flu H3N2
1977 Russian flu H1N1
2009 Swine flu H1N1
Next pandemic? Avian flu - 1997 H5N1 or H7N9
How do you diagnose an influenza infection?
Classic flu Sx in winters, current epidemiology
Also: serology, PCR, culture
What is the treatment for the flu?
Mostly supportive
Rx: Neuraminidase inhibitors
- oseltamivir - Tamiflu
- zananivir - Relenza
- IV peramivir - Rapivab
What could happen when aspirin is given to people/children <19 years with acute febrile illness?
Reye’s syndrome
- Aspirin or salicylates given to person
- Results in fatty liver and cerebral edema; can cause permanent brain/organ damage, liver problems, death
How are flu epidemics and pandemics prevented?
Yearly inactivated vaccines, generally given in the fall
Based on an epidemiological ‘forecast’ of the flu strains likely to be troublemakers in the flu season ahead
The flu is generally a mild and self-limiting disease. Why is it so problematic for immunocompromised people?
Infection can potentially compromise host further
- paves way for secondary infections, bacterial superinfections that could be much worse
What kind of genetic material does the Paramyxovirus family have? Envelope?
-ssRNA
enveloped
What 5 clinically important viruses are included in the family Paramyxovirus?
Parainfluenza
Mumps
Measles
Respiratory Synctial Virus (RSV)
Human metapneumovirus
What strange histological finding should you associate with the Paramyxovirus family?
Syncytia!
Produce multinucleated giant cells (syncytia) via a cell fusing factor
What is the point of the fusion protein for the Paramyxovirus family?
Fuses virus envelope to cell membrane
What surface glycoprotein is present in the Paramyxovirus family?
single surface HN glycoprotein with both hemagglutinin and neuraminidase activity
- this protein is lacking in metapneumovirus though
What pathology does human metapneumovirus cause?
Common cold, bronchiolitis and pneumonia in children and adults
How is an infection of human metapneumovirus dx’ed? How is it treated?
PCR - definitive
Also consider clinical presentation, obviously.
Treatment consists of supportive care.
What is the genetic makeup of parainfluenza viruses? Is it enveloped? How many serotypes?
-ssRNA, enveloped
4 serotypes, 1 and 2 are more severe
What tissues do parainfluenza viruses invade?
Local infection of ciliated respiratory epithelium
How widespread/common is infection from parainfluenza viruses?
Pretty common - cause of 30-40% of acute respiratory infection in infants and children
What are the symptoms of parainfluenza infection?
Mild cold-like to life-threatening (croup, bronchiolitis, pneumonia)
Most common cause of croup laryngotracheobronchitis (barking cough, steeple sign)
A young child presents with a recent Hx of febrile illness and a loud, barking cough like a seal. What do you suspect is causing the infection? What do you expect to see on a CXR?
seal bark cough = laryngotracheobronchitis = parainfluenza infection
Steeple sign on CXR - swelling and possible obstruction of airway in laryngotracheal region
What is the transmission of parainfluenza virus?
Droplet
How do you Dx and treat a suspected parainfluenza infection?
Dx - symptoms, then isolation of virus or serology
Rx - supportive care, isolation (keep kid home from day care or school)
contagious for 3-16 days
What is the genetic makeup of respiratory synctial virus (RSV)? Is it enveloped?
-ssRNA, enveloped
What tissues does RSV infect?
Local infection in ciliated epithelia (upper or lower respiratory tract), nose, eye and mouth
- can proceed into bronchioles, as per Dr. Gomez
What types of illness does RSV cause?
•Major cause of bronchiolitis and pneumonia in infants (#1 cause in age < 6 months)
Severe disease may present as bronchiolitis, pneumonia or croup
Reinfection in adults usually involves the upper respiratory tract (common cold
How common is infection and reinfection with RSV? How does it affect adults versus children/babies?
Extremely common, reinfection common
Worldwide, winter epidemics yearly
Reinfection in adults usually involves the upper respiratory tract (common cold)
Major cause of bronchiolitis and pneumonia in infants (#1 cause in age < 6 months)
Severe disease may present as bronchiolitis, pneumonia or croup
How do you Dx an RSV infection?
Strongly suspect in infants with lower respiratory tract infection.
Contagious about 4-5 days after the symptoms, so consider keeping children away from other children
Adults - usually presents as a cold
How do you care for an RSV infection?
•Rx - Supportive care and isolation
For sick infants consider Palivizumab - monoclonal antibody against F-protein
(Used in the prevention of RSV infections - F-protein is the factor that Paramyxovirus family viruses use to fuse virus envelope with host cell membrane. Could also slow spread of virus in vulnerable patients.)
What is the genetic makeup of the Mumps virus? Is it enveloped?
-ssRNA, enveloped
How is the Mumps virus spread?
Enters from salivary secretions (intimate contact) via the pharynx or conjunctiva
What tissues does the Mumps virus infect?
viremia targeting:
glandular (salivary glands, testes, ovaries, pancreas)
nerve tissue (causing aseptic meningitis and encephalitis)
An active Mumps infection will target glandular and nerve tissue. What sequelae can develop?
Asymptomatic in about 35%
Glands:
Painful enlargement of the salivary glands
Pancreatitis
Epididymoorchitis in males, which can cause sterility
Nerve:
Can produce transient high frequency deafness
What is the epidemiology of the Mumps virus? (How widespread, hosts, reservoirs, etc.)
- Found worldwide
- Epidemics every 2-7 years
- Humans only host
Generally more rare in countries with high vaccination rates - usually prevented by MMR
- babies can receive passive immunization from mom- IgA passed in breast milk, in utero, etc.
- children will usually only get mild form if vaccinated, as per Dr. Gomez
How do you Dx a Mumps infection? When is it contagious?
Does your patient resemble a bull frog?
- Dx- Classic clinical symptoms
- Disease is contagious just before and after the symptoms
- Incubation period is 18-21 days
- Serology, viral cultures and PCR also available
What is the treatment for a Mumps infection? How long is the patient contagious?
•Rx –Supportive care and isolation
- Disease is contagious just before and after the symptoms
- Incubation period is 18-21 days
How is infection with the mumps virus prevented?
•Prevention - Immunize with MMR live vaccine at 12-15 months and 4-6 years
Physicians can enhance immunity conferred from vaccine and reduce feelings of burnout by punching Andrew Wakefield and/or Jenny McCarthy in the face.
What is the genetic makeup of the measles virus? Is it enveloped?
-ssRNA, enveloped
What tissues does the measles virus infect?
•Enters oropharynx from human secretions
- followed by viremia to:
skin
mucosae
CNS
lymphatic &
respiratory systems
What symptoms, from mild to horrifying, can present when someone has a measles virus infection?
- Koplik spots of mouth precede T-cell mediated rash
- Usually have fever, maculopapular rash, +/- conjunctivitis that can lead to blindness, and sometimes pneumonia
- Inclusion body encephalitis and/or with chronic infection
subacute sclerosing panencephalitis (SSPE)
What is the epidemiology of the measles virus?
Extremely contagious!
Epidemics every 2-4 years in unvaccinated population of developed countries (93.3% vaccinated = herd immunity)
•Limited to humans and monkeys
•#1 cause of vaccine preventable deaths and illnesses
How is a Dx of measles virus infection made? What histological findings should you expect?
Dx -Typical clinical symptoms
Measles-specific IgM or viral RNA by PCR
multinucleated measles giant cells (Warthin-Finkeldey cells) with cytoplasmic and nuclear viral inclusions
How is a measles infection treated?
- Rx – Supportive, intramuscular immunoglobulin and isolation
- Contagious up to 4 days post rash
You are a physician and are lucky enough to practice in an area with high compliance to vaccination schedules. What threshold is needed for ‘herd immunity’ to measles virus? Should measles virus still be on your ‘radar’ as a source of morbidity and mortality for your patients?
herd immunity to measles - need 93.3% of pop. vaccinated (Colorado vaccination rate = 86%)
Individual cases of measles can still pop up, even in well-vaccinated populations
How is measles infection prevented?
- Immunize MMR live vaccine at 12-15 months and 4-6 years
What is the genomic makeup of hepatitis A? Is it enveloped? Classification?
+ssRNA, naked
Picornaviridae
What is the clinical presentation of a hepatitis A infection?
•Subclinical to fulminant hepatitis with rare chronic state in immunocompromised
What is the mode of transmission for hepatitis A?
Fecal oral route
How is a Dx made of a hepatitis A infection?
•Dx: Clinical presentation and or serology
What relevant serology findings should you expect for a hepatitis A infection?
Vaccinated person: +/- for anti-HAV IgG
Previous hepatitis A infection: + for anti-HAV IgG
Acute hepatitis A infection: + for anti-HAV IgM
How is hepatitis A infection prevented?
Hepatitis A vaccine - 2 doses
hygeine
What is the genomic makeup of hepatitis B? Is it enveloped? Classification?
dsDNA, enveloped
Hepadnaviridae
What is the clinical presentation of a hepatitis B infection?
- 1.Chronic persistent: Generally asymptomatic with a mild elevation of ALT
- 2.Chronic active: Jaundice, elevated liver enzymes, cirrhosis, +/- hepatocellular carcinoma
What is the mode of transmission for hepatitis B?
Parenteral, STI (Sexually Transmitted Infection)
What is the incubation period for hepatitis B?
60-180 days
What kind of virus is hepatitis B?
Hepatitis B = Dane particle - Oncogenic transforming virus
How is a hepatitis B infection Dx’ed?
Clinical presentation and serology:
B Vaccine: + HBsAb IgG
Previous B: -HBsAg, + HBcAb IgG, +/-HBcAb IgM, + HBsAb IgG, +/- Anti-HBe
B “window”: + HBcAb IgM, +/- HBsAb IgG, +/- Anti-HBe
Acute B: + HBsAg, + HBcAb IgG, + HBcAb IgM, + anti-HBe
Chronic B: + HBsAg, + HBcAb IgG, +/- anti-HBe
Chronic B + D Superinfection: + HBsAg, + HBcAb IgG, +/- HBcAb IgM, - HBsAbIgG, + anti-HDV
B & D Co-infection: + HBsAg, + HBcAb IgG, + HBcAb IgM, + anti-HDV
What is the expected serology of someone who is the recipient of the Hepatitis B vaccine?
B Vaccine: + HBsAb IgG
What is the expected serology of someone who has had a previous hepatitis B infection?
Previous B: -HBsAg, + HBcAb IgG, +/-HBcAb IgM, + HBsAb IgG, +/- Anti-HBe
What is the expected serology of someone who is in a hepatitis B infection “window”?
B “window”: + HBcAb IgM, +/- HBsAb IgG, +/- Anti-HBe
What is the expected serology of someone who is in an acute hepatitis B infection?
Acute B: + HBsAg, + HBcAb IgG, + HBcAb IgM, + anti-HBe
What is the expected serology of someone who is in a chronic hepatitis B infection?
Chronic B: + HBsAg, + HBcAb IgG, +/- anti-HBe
What is the expected serology of someone who is in a chronic hepatitis B & D superinfection?
Chronic B + D Superinfection: + HBsAg, + HBcAb IgG, +/- HBcAb IgM, - HBsAbIgG, + anti-HDV
What is the expected serology of someone who is in a hepatitis B & D coinfection?
B & D Co-infection: + HBsAg, + HBcAb IgG, + HBcAb IgM, + anti-HDV
How is a hepatitis B infection treated?
Supportive care
Nucleoside analogs and interferon for chronic hepatitis B
How is a hepatitis B infection prevented?
Safe needle and sex practices
Maternofetal/vertical infection prevention
3 doses hepatitis B vaccine
What is the genetic makeup of hepatitis C? Is it enveloped?
Flaviviridae
+ssRNA, enveloped
What is the mode of transmission for hepatitis C?
sex, parenteral
What is the incubation period for hepatitis C?
28-112 days
What hepatitis viruses are carrier states and asymptomatic infections common?
Hepatitis B, C, and D
What happens with a chronic persistent hepatitis C infection?
•1.Chronic persistent: Generally asymptomatic with a mild elevation of serum alanine transaminase (ALT)
What happens with a chronic active hepatitis C infection? What characteristics of the hepatitis C virus cause some of the more disastrous outcomes?
•2.Chronic active: Jaundice with elevated liver enzymes, cirrhosis and hepatocellular carcinoma
Hepatitis C- Oncogenic transforming virus
What are some medications that are helpful in controlling a hepatitis C infection?
•Rx – Harvoni (ledipasvir + sofosbuvir) or Sovaldi (sofosbuvir)+other antivirals (ribavirin)
How is a Dx of a hepatitis C infection made?
- Dx: Clinical presentation and or serology (more on next slide)
- C: Anti hepatitis C antibodies and HCV-RNA
What is the expected serology for a prior hepatitis C, acute C, and chronic hepatitis C infection?
Prior C: + anti-HCV
Acute C: + anti HCV, + HCV-RNA
Chronic C: + anti HCV, + HCV-RNA
What is the genetic makeup of a hepatitis D virus? Envelope?
-ssRNA (circular)
hepatitis B envelope
How is the hepatitis D virus transmitted?
parenteral, sex
Hepatitis D is unusual because it needs other entities in order to establish an infection. What does it need?
Hepatitis D (delta antigen)
- Have to have previous chronic or concurrent hepatitis B infection
- Defective incomplete virus - needs HBsAg for its own virion coat (envelope)
What are the symptoms of a hepatitis D infection?
•Presents with acute liver inflammation/failure, and jaundice
How is a Dx of a hepatitis D infection made?
Dx: Clinical presentation and or serology
•D: Anti-delta antibodies (Anti-HDV)
How is a hepatitis C infection treated?
Ribavirin (guanosine analog), protease NS3 inhibitors and interferon for chronic hepatitis C
How is hepatitis D infection prevented?
safe sex and needle practices
prevention of vertical transmission
What is the genetic makeup of a hepatitis E virus? Envelope? Classification?
Hepeviridae
+ssRNA
Naked - not enveloped
What pathology does hepatitis E cause? Where is it common?
- Subclinical to fulminant hepatitis with rare chronic state in immunocompromised
- Worldwide but more common in Asia and Africa
How is a Dx of a hepatitis E infection made?
Clinical presentation and serology:
•E: Anti hepatitis E antibodies and HEV-RNA
How is hepatitis E infection prevented?
Usually transmitted via fecal-oral route, so hygeine is key
What is the expected serology of a hepatitis E infection?
+ anti-HEV HEV RNA
In the interest of avoiding stupid rote memorization, what do the markers in hepatitis B serology tests actually mean?
HBsAg - Hepatitis surface antigen - indicates active infection, presence of virus in blood
anti-HBs - Hepatitis B surface antigen antibody - often IgG, signals someone has recovered from Hep B infection successfully, or has had the Hep B vaccine
anti-HBc - Total Hepatitis B core antibody - present at start of infection, remains for life. Indicates previous or current infection with Hep B.
anti-HBc IgM - Ab to Hepatitis B core antigen - indicates recent/acute infection with Hepatitis B.
