1
Q
What does it mean for an RNA virus to be “positive sense”?
Where do these viruses replicate?
A
- Means that the RNA is JUST LIKE a mRNA, it is ready for translation and does not need to bring along extra machinery (solely uses host machinery)
- In general, all positive-sense RNA viruses replicate in the cytoplasm
2
Q
All negative-sense RNA viruses are single stranded except _____
What are the viruses included in this viral family?
A
- Reovirus; including rotavirus and colorado tick fever virus
3
Q
What does it mean for an RNA virus to be “negative sense”?
A
- When they enter cell are not able to begin translation immediately.
- Must first be transcribed into a postive (+) strand of RNA (like mRNA)
- The negative-sense RNA virus MUST carry, in their capsid, an enzyme called RNA-dependent RNA polymerase
4
Q
CSF findings in aseptic (nonbacterial) meningitis (i.e., glucose, organisms, and protein)?
A
- Normal glucose
- No organisms
- Elevated protein
5
Q
What are the TORCHeS infection?
A
- Cross the placenta and cause infection in utero –> Congenital disease
- T = toxoplasma
- O = other
- R = rubella
- C = CMV
- H = HIV and HSV
- S = Syphillis
6
Q
What are the 4 segmented viruses? (hint: there is a mnemonic)
What is their significance?
A
- BOAR:
- Bunyavirus
- Orthomyxovirus
- Arenavirus
- Reovirus
* Segmented viruses undergo antigenic variation!
7
Q
What are the 2 types of mutations associated with antigenic variation of viruses?
Which leads to epidemics and which leads to pandemics?
A
- Antigenic drift: point mutations in HA or NA, associated with epidemics (this is the reason for new flu shot each year)
- Antigenic shift: reassortment of different combos of HA and NA leading to new species; associated with PANDEMICS
8
Q
What type of antigenic variation can occur with Influenza A and Influenza B; which is associated with ?
A
- Influenza A: most important = cause of EPIdemicsandpandemics;can undergoantigenic driftandantigenic shift(Has ‘A’ in the name so can undergo both types of ‘A‘ntigenic variation!)
- Influenza B: associated with endemic outbreaks; can ONLY undego antigenic drift
9
Q
Why is aspirin contraindicated in kids with suspected viral illnesses (i.e., Influenza or varicella)?
What is the pathogenesis?
A
- Can lead to Reyes syndrome — characterized by fever, rash, vomiting, liver failure, and encephalitis (can be fatal)
- Result of OxPhos uncoupling in hepatocyte mitochondria
10
Q
Where do viruses replicate in host cells (in general)?
A
- DNA virsues in the nucleus
- RNA viruses in the cytoplasm
11
Q
What are the general characteristic of the Picornavirus family?
What is the main form of transmission and the one exception?
A
- Positive-sense RNA virus
- Naked (lack envelope)
- Transmission: fecal-oral
- Exception is Rhinovirus: transmitted thru respiratory droplets
12
Q
What are the 3 clinical subgroups of the Picornavirus family and the viruses included in each?
A
- Hepatitis A —> hepatosplenomegaly
- Enteroviruses (poliovirus, coxsackie A and B, echovirus)
- Rhinovirus —> common cold
13
Q
What are characteristics of Poliovirus and what virus family does it belong to?
How does it survive in the GI upon entering the body?
A
- Part of the picornavirus family (Positive-sense, naked, RNA virus)
- Acid stable = fecal-oral transmission and can survive in GI tract
14
Q
What is the pathogenesis of Poliovirus once inside the body?
Where does it replicate and what are the clinical manifestations once it spreads?
A
- Initially replicates in lymphoid tissue, like tonsils and Peyer’s pathches (takes about 2-3 weeks)
- Spreads to anterior horn of spinal cord causing ASYMMETRIC paralysis (often of LEs)
- Also causes myalgias, decreased DTRs, aseptic meningitis, and respiratory insufficiency due to paralysis of diaphragm
15
Q
What family is Coxsackie A virus part of?
What are the 2 clinical manifestations?
A
- Picornafamily (SS Positive-sense, naked, RNA virus)
- Hepangina: mild self-limiting illness: fever, sore throat, and small red-based vesicle over back of throat
- Hand, foot, and mouth syndrome: common in children: fever, oral vesicles, and small tender lesions on the hands, feet, and buttocks
16
Q
What family is Coxsackie B virus part of?
What are the 2 important clinical manifestations?
A
- Picornavirus family (SS Positive-sense, naked RNA virus)
- Pleurodynia: fever, headache, and severe lower thoracic pain on breathing (aka Devil’s Grip)
- Myocarditis/Pericarditis: infection and inflammation of the heart muscle and pericarial membrane, can cause chest pain, arrhythmias, dilated cardiomyopathy, and heart failure
17
Q
What virus family is Rhinovirus a part of?
How is it transmitted and is it acid stable or labile?
A
- Picornavirus family (SS Postive-sense, naked, RNA virus)
- Acid labile, so is transmitted via inhalation of respiratory droplets
18
Q
What are the 2 viruses that can cause the common cold?
A
1) Rhinovirus
2) Coronaviridae
*A rhino drinking a corona!
19
Q
Hepatitis A is part of what viral family and has what characteristics?
How is it transmitted?
What are sources of contamination?
A
- Picornavirus family (Naked icosahedral capsid w/ positive-sense SS RNA)
- Is acid stable, so transmitted fecal-to-oral route
- Contaminated food or water, or close person-to-person contact (day care centers)
20
Q
What are the clinical manifestations of acute viral hepatitis A infection in adults and in children?
How long does the infection last?
A
- Children are infected most frequently and have milder sx’s, often NO JAUNDICE or even symptoms
- Adults: may have fever, flu-like sx’s, hepatomegaly, and jaundice
- Ususally lasts one month
21
Q
What does anti-HAV IgM in the serum mean?
anti-HAV IgG?
A
- anti-HAV IgM in serum = active Hepatitis A infection
- anti-HAV IgG in seum = indicates old infection and NO active disease
22
Q
What are the characteristics of Caliciviruses (norovirus)?
How is it transmitted?
Where is it commonly seen?
A
- Naked SS Positive-sense RNA virus
- Fecal-to-oral route
- Commonly seen on cruise ships and in day care centers
23
Q
What is the clinical presentation for infection by Calicivirus (norovirus)?
A
- Acute viral gastroenteritis: fever, vomiting, adbominal pain
- Explosive watery diarrhea
24
Q
What are the characteristics of the Flaviviridae family of viruses?
A
- Positive-sense SS RNA virus
- ENVELOPED
- Non-segmented
25
What 6 diseases are caused by the Flaviviridae family of viruses?
- Hepatitis C
- Dengue fever
- Yellow fever
- West Nile Virus
- St. Louis and Japanses encephalitis
26
What are the characteristics of the Flavivirus: Dengue fever?
How is it transmitted?
Which serotype is the most serious?
- Mosquitos are the **vector**
- Called **break-bone fever**: severe painful backache, muscle and joint pain, and severe headache
- Repeat infection w/ **Serotype 2** causes **Dengue hemorrhagic fever** --\> hemorrhage, thrombocytopenia, and **shock**
27
What are the characteristics of the Flavivirus: Yellow fever?
How is it transmitted?
- Mosquitos are the **vector**
- Hepatitis w/ jaundice, fever, bachache, nausea, and vomiting
28
Clinical features of the Flavivirus: West Nile virus including reservoir and vector, major complication, and diagnosis
- Reservoir = birds
- Vector = mosquitos
- Major complications = **aseptic meningitis, frank encephalitis** w/ decreased levels of consiousness, and/or **dramatic motor paresis/flaccid paralysis**
- **Dx:** PCR, serology (IgM versus WNV), or CSF (w/ IgM against WNV)
29
Hepatitis C is a member of what virus family?
How is it transmitted?
- Flavivirus family (Enveloped, positive-sense RNA virus)
- Transmitted **parenterally**, blood-to-blood (blood transfusions, needle sticks, IV drug use, placentally, or sex)
30
What are the clinical manifestations of Hepatitis C infection (both acute and chronic)?
Which associated cancer?
**Acute** = usually asymptomatic, but some have fever, nausea, muscle aches, hepatomegaly, RUQ pain, and jaundice
- Up to **85%** of patients will develop **chronic** **hepatitis;** which can evenutally lead to **cirrhosis**
- Primary cause of **Hepatocellular carcinoma**
**\***Think the 'C' in Hep C stands for **Chronic!**
31
What is the leading cause of chronic hepatitis in the U.S.?
What is the leading indication for liver transplantation in U.S.?
- **Hep C** is leading cause of **chronic hepatitis**
- **Chronic Hep C** is leading indication for **liver transplant**
32
How is infection with Hepatitis C diagnosed?
- Testing for **anti-HVC Abs** detectable within 6-8 wks post-exposure
- Positive test confirmed via RIBA or by measuring the HCV viral RNA
33
Which 3 virus families are Arboviruses?
1) Bunyaviridae
2) Togoviridae
3) Flaviviridae
\*Means they have an arthropod vector (i.e., mosquitos)
34
What are the characteristics of the Togaviridae family?
Most transmitted how?
Which viruses are in this family?
- **Enveloped**, Positive-sense, SS RNA virus
- Transmitted via **arthropod (**except Rubella**)**
- **Wester, Eastern,** and **Venezuelan equnie encephalitis** = Alpha viruses
**- Rubivirus** = Rubella = NOT an Arbovirus
35
How is Rubivirus transmitted and what disease does it cause?
- Rubella (AKA "German Measles)
- Respiratory transmission
- Can also cross the placenta ---\> **congenital rubella**
36
What are the characteristics of Childhood Rubella infection?
What type of rash?
How long does it last?
- Tender postauricular and occipital lymphadenopathy + Fever
- **Maculopapular** rash that **begins** on **Forehead/****face**and spreads to**torso**and**extremities**
- Lasts **only 3 days!**
37
What are the clinical manifestations of Congenital Rubella; especially if virus crosses placenta in the first trimester? (Heart, eyes, and CNS)
The classic triad?
1) **Heart**: PDA, interventricular septal defects, pulmonary stenosis
2) **Eye:** cataracts, chorioretinitis, blindness
3) **CNS:** mental retardation, microcephaly, and deafness
**Classic triad:** Congenital cataracts, sensory-neural deafness, and PDA
38
Young women infected with Rubella may develop?
Self-limiting **arthritis**
39
What are the characteristics of Coronavirus?
What is a unique characteristic of its morphology?
- Positive-sense, SS RNA virus
- Encapsulated
- **Helical**
40
What are the clinical manifestations of Coronavirus?
What is the most recent novel virus in this family and its manifestations and how can it be diagnosed?
- Cause of the **common cold**
- **SARS:** fever, myalgias, and chills, and later develop a dry cough, chest pain, SOB, which can progress to **ARDS**
- Dx: using PCR or seroconversion (detecting Abs in blood to the virus)
41
What are the morphological characteristics of HIV and what does it do inside of cells?
- **Diploid**, Positive-sense SS RNA virus that gets converted to **DNA intermediate** by **reverse transcriptase** and then encorporated into **host chromosomes**
- **Enveloped**
42
What are the 3 important genetic components of HIV and what does each gene make?
1) **gag** = **p24** which is the **major capsid protein**
2) **pol** = **reverse transcriptase**
3) **env** = gp41 (transmembrane protein) and **gp120** (outer glycoprotein)
43
When an AIDS patients CD4+ T cell counts are \<200 serious opportunistic infections by which 3 organisms may occur?
- *Pneumocystis carnii* pneumonia
- *Cryptococcus neoformans*
- *Toxoplasma gondii*
44
When and AIDS patient's CD4+ T cell counts are \<50 which organisms may cause disease?
- *Mycobacterium avium-intracellulare*, normally only affecting birds, causes disseminated disease in AIDS patients
- Cytomegalovirus infections also rise
45
What is the screening test for AIDS?
Confirmed how?
- ELISA screen for HIV
- Confirmation via **Western Blot**
46
What are the 3 major malignancies associated with AIDS?
1) **B-cell lymphoma** often in the brain
2) **Kaposi's sarcoma**
3) **Invasive cervical cancer** (with related HPV co-infection)
47
Which 2 fungi produce disseminated disease in AIDS patients?
1) *Histoplasma capsulatum* (Mississippi and Ohio River Valleys)
2) *Coccidioides immitis* (Southwestern U.S)
48
What are the characteristics of Orthomyxovirus; why is it **unique**?
- Negative-sense SS RNA
- Lipid containing **envelope**
- **Replicates in the NUCLEUS! (an exception)**
- Segmented (**7-8**)
49
What are the 2 virulence factors of Orthomyxovirus?
1) **Hemagglutinin (HA):** binds **sialic acid receptors** on RBCs and cells of the upper respiratory tract; causes fusion between host cell membrane and virion membrane = dumping of viral genome into host cell
2) **Neuraminidase (NA):** breaks down neuraminic acid, important components of mucin, exposing sialic acid binding sites beneath
50
What is the difference between influenza A and B in terms of antigenic variation?
- **A** is most important because it undergoes both antigenic **DRIFT** and **SHIFT**, thus it is the cause of epidemics and pandemics
- **B** undergoes just antigenic **DRIFT**, so it is associated with endemics
51
Although the common cold and influenza (the flu) have very similar symptoms, what really sets apart viral influenza infection?
Painful muscle aches
High fevers
Headaches
52
Influenza can cause a primary pneumonia, or weaken the immunity to promote a delayed secondary bacterial pneumonia or otitis media with which 3 main bacteria?
1) *Staphylococcus aureus*
2) *Haemophilus influenzae*
3) *Streptococcus pneumoniae*
53
What is H5N1 and how are people typically exposed?
Nearly all patients infected with this strain have what clinical manifestations?
- Bird-flu
- Plucking and preparing diseased chickens or ducks, handling fighting cocks, or playing w/ asymptomatic ducks
- Develop a **clinical pneumonia** w/ **diffuse patchy infiltrates** on chest radiogram which progress to **consolidation** w/ **air-bronchograms** in **more than one lung zone**
- Rapidly progressed to **ARDS or non-cardiogenic pulmonary edema**
54
What are the characteristics of Paramyxovirus?
Transmission how?
- Negative-sense SS RNA virus
- Enveloped
- **NOT** segmented
- Transmission = **respiratory droplets**
55
What are 4 important viruses in the Paramyxovirus family?
1) Parainfluenza
2) Respiratory syncytial virus
3) Mumps
4) Measles
56
What are the clinical manifestations of the Paramyxovirus: Measles (aka **rubeola**)?
Characteristic findings?
- Prior to rash, pt suffers prodromal illness w/ **conjunctivitis**, swelling of eyelids, photophobia, **HIGH** **fevers** (105 F), and **hacking cough**
- 1-2 days before rash, **Koplik's Spots** develop = small red-based lesions w/ blue white center in mouth
- **Maculopapular rash** begins on forhead/face and spreads to neck before **traveling down** to rest of the body; lasts **6 days**
**\*4 "C's" = Cough, Coryza** (runny/stuffy nose), **Conjunctivitis, Koplik** **spots**
57
What are some of the serious complications associated with measles (rubeola)?
What is the most serious late-onset complication?
- Pneumonia, eye damage, heart involvement (myocarditis)
- **Subacute sclerosis panencephalitis (SSPE)**: slow forming encephalitis, which presents **many years** after measles infection w/ slowly progressing CNS disease, mental deterioration and incoordination
58
What virulence factor do paramyxoviruses contain that is not present in orthomyxoviruses and causes host cells to fuse?
What do they form?
- Posses a **fusion (F) protein**
- Multinucleated giant cells (**syncytial cells**)
59
What kind of special cell formation is a characteristic of measles (rubeola)?
**Warthin-Finkeldey cells**, randomly distributed multinucleate giant cells
60
What are the classic signs and characteristics of the Paramyxovirus: Parainfluenza Virus?
- **Croup**: infection of the larnyx and other upper respiratory structures (l**aryngotracheobronchitis**)
- Swelling of these structures narrows airways -\> **Stridor** (wheezing sound) and a **barking cough** (like a **seal**)
61
Which virulence factors does Parainfluenza virus have?
All 3 VF's: **fusion protein, HA, and NA**
62
Which virulence factors does Measles virus (rubeola) have?
1. HA **only**
2. **F-protein**
63
What is the clinical presentation for the Paramyxovirus: Mumps?
What complications can occur?
Which virulence factors does this virus have?
- Infection most frequently in the **PAROTID glands**, which **swell and become painful**
- The **TESTES** are also frequently infected and can sometimes progress to **orchitis** (inflammation of **epididymis**) and in rare cases **infertility**
- Meningitis and encephalitis may occur
- VFs = **HA, NA,** and **F protein (ALL 3!)**
64
What are the clinical features of the Paramyxovirus: Respiratory Syncytial Virus (RSV)?
In terms of VFs why is this virus unique?
- **#1 cause of pneumonia** in young children, **especially infants \< 6 mo.**
**- Acute otitis media** occurs in up to 33% of children
**-** Only has **Fusion (****F) protein**as a VF, which causes formation of**multinucleated giant cells (syncytial cells)**
65
What are the morphological characteristics of Rhabdovirus?
What is the classic shape it is described as?
Most common reservoir?
- Negative-sense SS RNA
- **Helical** nucleocapsid coiled into a **BULLET** shape
- **Enveloped**
- **Bats**, but all warm-blooded aminals can be carriers
66
What occurs when a human is bitten and infected with Rabies virus?
How do they symptoms progress?
- Virus replicates locally at the wound site for a few days, and then migrates **slowly** (weeks to years) up nerve axons to the CNS
- First sx's are fever, headache, sore throat, fatigue, and painfully sensitive nerve around the healed wound
- **Acute encephalitis:** hyperactivity and agitation lead to confusion, meningismus and even seizures
- **Class brainstem encephalitis**: cause CN dysfunction and painful contraction of pharyngeal muscle --\> dysphagia --\> foaming from mouth
- **Death** occurs secondary to **respiratory dysfunction**
67
Brain cells in rabies demonstrate neuropathic changes and what characteristic finding?
Collections of virions in the cytoplasm of neurons called **Negri bodies**
68
What are the morphologic characteristics of Filoviruses?
- Negative-sense SS RNA virus
- **Helical** symmetry
- Enveloped
69
What are the Filoviruses and how are they transmitted?
Who is at greatest risk?
- **Ebola** and **Marburg virus**
- Transmission via **direct contact** w/ **bodily fluids**
- Healthcare workers and family members of infected individual
70
What is the clinical presentation of infection with the Filovirus: Ebola?
- Abrupt onset of fever, chills, and malaise; nausea, vomiting, and abdominal pain within first few days
- Petechial rash may develop around days 5-7
- May progress to **hemorrhagic fever --\> end organ failure --\> severe blood loss --\> hypovolemic shock** and **death**
71
What are the morphological characteristics of Bunyaviruses?
What is the vector for these virus; the one exception is?
- Negative-sense SS RNA virus
- **Segmented (3 segments) - BOAR**
- **Helical**
- Arthropod vector; except for **Hantavirus** (deer mouse)
72
Which viruses are part of the Bunyavirus family?
- California encephalitis virus
- Rift Valley fever virus
- Sandfly fever virus
- Hantavirus
73
The Bunyaviruses: California encephalitis virus, Rift Valley fever virus, and Sandfly fever virus share similar clinical manifestations, what are they?
- Fever and encephalitis
- Rift valley fever can also cause hemorrhagic manifestations
74
What are the clinical manifestation of the Bunyavirus: Hantavirus?
What is the reservoir and mode of transmission?
- Deer mouse is the primary vector
- Pulmonary edema via capillary leak --\> Respiratory failure
- Pre-renal azotemia
- Hemorrhagic fever
75
A 21 yo man presents to the clinic with influenza-like symptoms, but within a few hours develops pulmonary edema.
What virus is this most consistent with?
Hantavirus (Bunyaviridae family)
76
What are the morphological characteristics of Arenaviruses?
- Negative-sense SS RNA virus
- **Segmented (2 segments) BOAR!**
- Helical
- Enveloped
77
Which viruses are in the Arenavirus family?
How are they transmitted?
- Lymphocytic choriomeningitis virus (**LMV**)
- Lassa virus
- South American hemorrhagic fever viruses
- **Transmission** = contact w/ **rodent urine**
78
Which viruses that cause hemorrhagic fever are known to have been weaponized?
- Ebola
- Marburg virus
- Rift Valley Fever
- Yellow Fever Virus
79
What are the clinical manifestations of the Arenaviruses: Lassa Fever Virus and South American Hemorrhagic Fever Virus?
- **Lassa Fever:** fever, sore throat, abdominal pain, with intractable vomiting and hypotension
- **South American:** gradual onset of fever, myalgias, nausea, abdominal pain. Later, **bleeding/petechiae**. Sometimes tremor, seizure, diarrhea
80
Reoviridae characteristics (rotavirus, colorado tick fever virus); why is this virus unique??
How is this virus transmitted?
- **Double-stranded RNA virus!**
**- Segmented (11 segments) - BOAR**
**- Naked**
- Transmission: **fecal-oral,** except CTFV is by a **tick**
81
What are the clinical manifestations of the Reovirus: Rotavirus?
- **Viral gastroenteritis:** profound dehydration, especially in infants,
- Fever, abdominal pain, vomiting and diarrhea (NO blood)
- **Major cause** of infant death (under-developed countries) and most common cause of diarrhea in infants less than 3 y/o
82
What is the toxin associated with Reovirus and what are its pathogenic effects?
- Enterotoxin = NSP4
- Induces epithelial apoptosis causing a net secretion of water and electrolytes causes a **watery explosive diarrhea**
83
How is the Colorado tick virus differentiated from Rocky Mountain Fever?
- Fever, vomiting, myalgia, but **NO RASH**
84
What 7 viruses are included in the Herpesviridae family?
1) HSV-1
2) HSV-2
3) Varicella-zoster virus
4) Cytomegalovirus
5) EBV
6) HHV-6
7) HHV-8
85
What are the morphological characteristics of all the Herpesviridae?
- Double-stranded linear DNA
- Enveloped
- Icosahedral
86
What classic morphology is seen in HSV-infected cell?
Also seen in what other viruses in this family?
Large, pink-purple **intranuclear inclusions** (**Cowdry bodies**)
\*Also seen in **CMV** and **VZV**
87
What is the 1st clinical sign of an infection with HSV-1?
How does it progress and what other clinical manifestations may occur?
- Gingivostomatitis = 1st
- Eventually just Herpes labialis = Cold sores
- Can develop **herpetic keratitis, encephalitis (#1 viral cause),** or in immune compromised there may be **dissemination** to organs
88
Where does HSV 1 vs. HSV 2 remain latent/dormant
HSV-1 = trigeminal ganglia
HSV-2 = sacral ganglia
89
What is Herpetic Whitlow?
- HSV infection of the finger, becomes painful, red, hot and swollen
- Sometimes seen in **dental workers**
90
A sexually active patient presents w/ a painful, vesicular rash and ulceration of the genitals. You also note painful inguinal LAD.
What do you suspect?
HSV-2
91
What affect can herpes have on a fetus in utero?
- Is a **TORCHeS infection**
- Can cause congenital defects or intrauterine death
92
How is EBV (herpesviridae) transmitted?
What cells does it infect and where is its site of latency?
- Transmitted by close human contact, most frequently through the saliva during kissing (causes mono)
- Infects B-cell by binding to **CD21 (CR2)** the receptor for **C3d**
- Latent in B cells
93
The response of which cells of the immune system are most important for the symptoms of infectious mononucleosis caused by EBV?
CD8+ CTL and NK cells
94
What are the clinical manifestations of infectious mononucleosis caused by EBV?
What age group does it affect most?
- Fever, chills, sweats, headache, and **very painful pharyngitis**
- **Enlarged LNs and Spleen** are **common**
- A disease of **young adults**
95
EBV is associated with what 3 cancers?
1) Nasopharyngeal carcinoma (Asian)
2) Hodgikin's lymphoma
3) Burkitt lymphoma (particularly in Africa)
96
Blood work of someone with infectious mononucleosis will reveal?
Blood smear?
What is a rapid laboratory test for diagnosis?
- High WBC count with **atypical lymphocytes** on **blood smear**
- **Monospot test =** infected pt's blood has **heterophile antibody**, against EBV that cross reacts w/ and **agglutinates sheep RBCs** = **rapid test**
97
EBV is associated with what manifestation of the tongue in patients with HIV?
- Oral-hairy leukoplakia
- Looks like candida but cant be scraped off
98
CMV (Herpesviridiae family) is transmitted how?
Remains latent in which cell?
- **Transmitted** via blood, sex, breast milk, saliva, urine and transplacentally (TORCHeS)
- Remains **latent** in **mononuclear leukocytes = B and T cell, Macrophages**
99
How can the mononucleosis caused by CMV being differentiated from the once caused by EBV?
Patients w/ CMV as the cause of their mononucleosis syndrome will have "**Monospot negative mono**"
100
What are the clinical manifestations of congenital CMV infection?
How can this virus cause problems later in life?
- 80-90% are **asymptomatic**
- 15% will later develop progressive unilateral or bilateral **hearing loss**
- Affected infants may suffer intrauterine growth retardation, and present w/ **blueberry muffin** rash (caused by thrombocytopenia), **jaundice, and hepatosplenomegaly, anemia,** and **encephalitis**
101
Which population of immunosuppressed patients are at high risk of developing CMV pneumonitis, as well as CMV verimia and colitis?
Organ transplant patients
102
Which immunocompromised population is at a high risk of developing CMV retinitis and CMV colitis, but rarely CMV pneumonia?
AIDS patients
103
Strikingly enlarged cells with prominent intranuclear basophilic inclusions is characteristic of what virus?
CMV
104
What are 3 ways/tests for diagnosing CMV infections?
1) **Buffy coat culture:** since CMV invades WBCs
2) Detection of **CMV Ag** in the blood
3) **PCR**: to detect CMV DNA
105
Varicella-Zoster Virus (herpesviridae family) causes what 2 disases?
- Varicella (**chickenpox**)
- Herpes zoster (**shingles**)
106
How is Varicella Zoster virus transmitted?
What occurs when someone becomes infected?
Describe the characteristics of the rash?
- Respiratory droplets
- Fever, malaise, and headache are followed by a rash
- Starts on the face and trunk, spreading to the entire body, including mucous membranes (pharynx, vagina, etc.)
- Described as **"dew drops on a rose" rash**
- Multiple vesicles arise in patches (crops), and one crop will form as another crop scabs over = **lesions in different stages!**
107
VZV remains latent where?
Dorsal root ganglia
108
How would you differentiate chickenpox rash from smallpox rahs?
- **VZV (chickenpox)** has lesions at **different stages of healing + superficial**
- **Smallpox** lesions are at the **SAME stage** and **ulcerate** **deep**
109
Adult presentation of VZV infection?
Higher risk of?
- Pneumonia (**high risk**), encephalitis (note that these can be presentations in kids too)
- Adults typically contract in immunocompromised state
110
VZV lies dormant in dorsal root ganglia. It may be reactivated with aging, stress, or immunocompromised state and cause what disease?
What are the clinical features?
What occurs after the rash subsides?
**- Shingles (herpes zoster)**
- “Dew drops on a rose” rash in dermatomal distribution (**rarely** crosses midline — if it does you must test for HIV)
- **E****xtremely painful, intense itching,** and burning
- Once rash subsides you have **postherpetic neuralgia** = pain w/o rash
111
What cells does HHV-6 infect and what disease does it cause?
Primarily affects which age group?
- Infects **CD4+ Helper T cell** --\> can cause immunosuppression by killing off these cells
- Causes **Roseola (aka Exanthum subitum):** primarily affected **children** between **6 mo. - 2 years**
112
What are the clinical manifestations of Roseola (Exanthum subitem) caused by HHV-6?
What is the timeline of events?
- **Very** high **fever** lasting **3-5 days**, which resolves and is followed by:
- **Diffuse lacy maculopapular rash**, mostly on the trunk and spares the face, lasting for **1-2 days**
113
What does HHV-8 cause?
How is it transmitted?
Who's at greatest risk?
- Kaposi's Sarcoma
- Transmission via: sexual contact, kissing, and especially MSM
- Highest risk for: AIDS/immunocompromised, elderly Russian men, and areas of Africa
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Clinical features of HHV-8, Kaposi’s sarcoma (herpesviridae)?
Proliferation of vasculature through dysregulation of?
- Erythematous **violacious lesions** on nose, extemities, and mucous membranes may be present as plaque, patch, macule, or noduel
- MOST common location of lesions = **hard palate**
- Kaposi sarcoma causes **proliferation of vasculature** through dysregulation of **VEGF**
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HHV-8, Kaposi’s sarcoma (herpesviridae) may be confused with bacillary angiomatosus (bartonella hensleae bacterial infection). How are these 2 differentiated?
Need to examine lesions microscopically to differentiate:
- Kaposi’s has **lymphocytic infiltrate**
- Bacillary angiomatosus would show **neutrophilic infiltrate**
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Characteristics of Papovaridiae viruses, including polyomaviridae (JC polyomavirus, BK polyomavirus) and Papilloma virus (HPV)?
Circular, Naked, DS DNA viruses
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Clinical manifestations of JC virus (polyomaviridae) as an opportunistic infection in AIDS patients?
What CD4+ count is at risk for this disease?
- Causes **progressive multifocal leukoencephalopathy (PML)**
- Demyelinating disease of the CNS affecting **white matter**
- CD4+ \<200
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Clinical manifestations of BK virus (polyomaviridae) including patient population that this disease effects.
How does it affect children?
- **Nephritis** and **renal** stenosis in **renal transplant** patients
- **Hemorrhagic cystitis** in **bone marrow** transplant patients
- Causes **mild respiratory** illness in **children**
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Characteristics of papillomaviridae (HPV 6,11,16,18,31,33)?
What virus family does it belong to?
- Naked, Circular, DS DNA virus
- Papovaviridiae family
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Clinical manifestations of HPV 1-4
6 and 11?
16, 18?
HPV 1-4 = **common warts**
HPV 6 and 11 = **laryngeal papillomatosis** and **laryngeal warts**
HPV 16 and 18 = **cervical cancer (anogenital carcinomas)**
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Characteristics of parvovirus B19 (parvoviridae); what is unique about this virus?
- The **ONLY single-stranded linear DNA virus**
**- Smallest icosahedral virus**
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How is Parvovirus B19 transmitted and what diseases does it cause?
- Respiratory droplets and vertical transmission
- **Hydrops fetalis** if contracted in utero
- **Slapped cheek disease** (aka **Fifth disease** or **Erythema infectiosum**)
- **Transient aplasitc anemia crisis** in sickle cell patients
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What age group is most often affected by erythema infectiosum (aka Fifth or Slapped Cheek Disease)?
What occurs?
Caused by what virus?
- Children between **ages 4-12**
- Parvovirus B19 (only SS linear DNA virus!)
- Gets get a **low-grade fever**, lasts **one week**, fever breaks and child develops **slapped cheek rash on face****,** which can progress to lacy reticular pattern down the body
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Transient aplastic anemia crisis caused by Parvovirus B19 occurs when the virus does what?
What population is it often seen in?
- Occurs when Parvo virus stops the production of RBCs in bone marrow
- Sickle cell patients
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Characteristics of adenovirus (adenoviridae) including transmission
- DS linear DNA virus
- Naked virus
- Transmitted via respiratory droplets and fecal-oral
- Most commonly affects children, military recruits, and those who use **public pools**
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Clinical manifestations of adenovirus (adenoviridae)?
Most common cause of?
- Childhood URIs: **rhinitis, sore throat, fever, conjunctivitis**
- Most common cause of infection in the **adenoids and tonsils (tonsilitis)**
**- Epidemic keratoconjunctivitis (Pink eye)**
**- Epidemic diarrheal illness** in infants and children (enteric adenovirus)
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What are the characteristics of the Poxviridae family?
What makes this virus unique?
- DS DNA virus
- DNA is organized into a **DUMBBELL shape** w/ structural proteins, surrounded by **2 envelopes**
- Contains all its own machinery!
- **Only DNA virus** to replicate in **cytoplasm**
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What 2 diseases are caused by the Poxviridae virus?
- **Small pox**: causes skin lesions and death!
- **Molluscum contagiosum:** small white bumps w/ a **central dimple** (like a wart). Often found on **genital region**
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Which 3 enveloped, RNA viruses are the most important in terms of causing viral hemorrhagic fever and the ability to be used as agents of bioterrorism?
1. **Filoviruses:** Ebola and Marburg virus
2. **Bunyaviruses:** Crimean Congo Hemorrhagic Fever
3. **Arenaviruses:** Lassa Fever Viruses
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Morphologic characteristics of Hepatitis B virus (hepadnavirus)?
- Enveloped, DS circular DNA virus
- Carries a DNA polymerase enzyme within the virion (unique)
- Intact virus called **Dane particle**
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Transmission of Hep B virus
Sexual transmission, sharing blood products, or during delivery (does not cross placenta) - **extremely contagious**
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Serological tests help establish HBV infection, what is the relevance of HBsAg and anti-HBsAg?
- **HBsAg =** DISEASE (chronic or acute)
- **Anti-HBsAg** = IMMUNE, CURE, NO ACTIVE DISEASE!
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Serological tests help establish HBV infection, what is the relevance of IgM anti-HBcAg and IgG anti-HBcAg?
- **IgM anti-HBcAg** = **NEW infection**
## Footnote
**- IgG anti-HBcAg = OLD infection**
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Serological tests help establish HBV infection, what is the relevance of HBeAg and anti-HBeAg?
- **HBeAg = HIGH INFECTIVITY**
- **anti-HBeAg** = **LOW infectivity**
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Which patients are more likely to be asymptomatic carriers of HBV?
Why?
- Immunocompromised states, such as malnutrition, AIDS, and chronic illnesses
- Their immune system is too weak to attack
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What's the deal with Hepatitis D?
How is it transmitted and what does it rely on?
- **Incomplete RNA** virus-only infective w/ help from Hep B
- Helical nucleocapsid that requires the Hep B envelope (**HBsAg**) to be infectious
- Transmitted via: blood transfusion, needle sticks sex, or across placenta
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What are the 2 ways in which Hepatitis D infection can occur?
1) **Co-infection:** HBV and HDV are transmitted **together** parenterally and cause an **acute hepatitis**, similar to that of HBV. Abs to HBsAg will be protective against **both** and end infection
2) **Superinfection:** HDV infects a person who has **chronic HBV** infection = acute hepatits in pt already chronically infected with HBV. Often **severe**, with **high incidence** of **fulminant hepatitis, cirrhosis**, and **greater mortality**. Pt w/ chronic HBV cannot make Anti-HBsAg and so remains chronically infected with both
