Viruses Flashcards
1
Q
Hepatitis A
A
- a non-enveloped, positive strand RNA virus of the picorna family
- water, food, close contact transmission
- 30d incubation period with insidious onset of nausea, fever, malaise, elevated LFT, and juandice
- jaundice and mortality increase with age
- diagnosed with IgM
- 2 part vaccine available
2
Q
Hepatitis E
A
- a positive strand RNA virus of the hepe family
- outbreaks surround fecally contaminated water
- US cases usually have a history of travel
- mortality increases with age and pregnancy
- swine and avian reservoirs
- 40d incubation period
3
Q
Hepatitis C
A
- a positive strand RNA virus of flavi family
- types Ia, Ib, 2, and 3 most common in the US
- transmitted percutaneously and permucosally
- replicates, assembles at membranous web, can spread through basolateral membrane
- 6-7 week incubation period but acute infection goes unnoticed
- high incidence of chronic infection
- alcohol, >40, HIV, HBV, male all increase morbidity
4
Q
Describe the HepB genome.
A
- a relaxed circular DNA virus
- C gene encodes HBc and HBe antigens
- P gene encodes polymerase
- S gene encodes S, S1, S2
5
Q
Hepatitis B
A
- a relaxed circular DNA virus of the hepadna family
- genome can integrate into host genome
- transmitted perinatally, parenterally, and sexually
- 60-90d incubation period
- chronic complications more common in those <5 y.o.
- complications: HCC, PAN, glomerulonephritis, cirrhosis
- pathology is immune mediated
6
Q
Hepatitis D
A
- a ssRNA virus that replicates in the nucleus
- encodes only the gamma antigen
- reliant on HBV for surface antigen
- percutaneous and permucosal transmission
- co-infection more likely to resolve than superinfection
7
Q
List the modes of transmission for each of the hepatitis viruses.
A
A: food, water, close contact B: sexual, perinatal, parenteral C: percutaneous, permucosal D: percutaneous, permucosal E: fecally contaminated water
8
Q
List the common complications of Hepatitis B.
A
HCC, PAN, glomerulonephritis, cirrhosis
9
Q
Hepatitis B pathology is mediated by what?
A
immune mediated
10
Q
Which hepatitis virus assembles at the membranous web and can spread directly through the basolateral membrane of the host cell?
A
hepatitis C
11
Q
Which hepatitis virus has a relaxed circular DNA genome?
A
hepatitis B
12
Q
List the most common organisms associated with aseptic meningitis.
A
enteroviruses, primarily coxsackie A and B
13
Q
Describe the presentation of aseptic meningitis.
A
- headache, neck stiffness, photophobia
- fever lasting five days
- rash, diarrhea, and cough common in young children
- rash is erythematous, maculopapular, and vesicular on the soles of the hands and feet and on mucous membranes
14
Q
Poliovirus
A
- an serotype of enterovirus known to cause poliomyelitis
- has a tropism for the CNS but usually confined to oropharynx and gut
15
Q
What are the three possible outcomes of a poliovirus infection?
A
- asymptomatic or mild illness
- non-paralytic poliomyelitis or aseptic meningitis
- paralytic poliomyelitis
16
Q
Poliovirus targets which CNS cells.
A
autonomic and motor neurons of the anterior horn, pons, and medulla
17
Q
What kind of vaccine is currently in use against poliovirus?
A
an inactivated vaccine
18
Q
What happens in most cases of poliovirus infection?
A
90% of the time, the virus is confined to the gut and oropharynx and causes a mild illness of fever, malaise, and sore throat
19
Q
The picornaviridae family includes what organisms?
A
it is a group of GI viruses include the enterovirus and hepatovirus genera
20
Q
Describe the picornaviridae family genomes.
A
positive strand RNA viruses that yield a poly protein that must be cleaved
21
Q
Describe the life cycle of picornaviruses.
A
- rapid- taken up via receptor mediated endocytosis
- inhibits cellular translation so it favors viral translation
- released by cell lysis
22
Q
Which family of viruses has an incredibly rapid life cycle and inhibits host translation to favor viral translation?
A
picornaviruses
23
Q
The enteroviruses is a species within the ___ family that includes which four serotypes?
A
- part of the picornaviridae family
- includes coxsackie A and B, poliovirus, and echovirus
24
Q
The enteroviruses cause what diseases?
A
depending on the serotype:
- meningitis
- paralysis
- febrile exanthems
- ARD
- myocarditis
- orchitis
25
What role do secretory and serum antibodies play against enteroviruses?
secretory prevent initiation of infection while serum antibodies prevent viremic spread
26
What is the most common result of enteroviruses?
asymptomatic, mild URT disease, mild influenza-like disease
27
Enterovirus
- a species of the picorna family that includes coxsackie A and B, poliovirus, and echovirus
- enter via GI or respiratory tract and then enter lymphatics
- viral replication responsible for pathology
- rarely cause GI disease
- usually cause asymptomatic or mild flu-like illness
- can cause meningitis, orchitis, myocarditis, paralysis, ARD, or febrile exanthems
28
List the five GI virus families.
- picornaviridae
- rotaviridae
- caliciviridae
- astroviridae
- adenoviridae
29
Norwalk Virus
- a positive strand RNA GI virus of the caliciviridae family
- most common cause of gastroenteritis
- causes nausea, vomiting, anorexia, diarrhea, and headache after a 2-4 day incubation period
- common on cruise ships
- usually from contaminated food or water
- prevent with proper sanitation
30
What is the most common cause of gastroenteritis worldwide?
norwalk virus
31
Which virus is a common cause of GI problems on cruise ships?
norwalk virus
32
Describe the presentation of norwalk virus including incubation period.
- 2-4 day incubation period
| - nausea, vomiting, anorexia, diarrhea, headache
33
Astroviridae
a family of GI viruses associated with endemic gastroenteritis in young children and neonates
34
What mediates enterovirus pathology?
viral replication
35
What is the most significant cause of infantile diarrhea?
the rotavirus family
36
Describe the structure of rotavirus and its genome.
- triple layer capsid (inner VP6 determines classification, outer VP4, VP7)
- dsRNA virus with 11 segments
37
What is the most common rotavirus?
group A, G1P[8]
38
How does rotavirus spread?
oral-fecal route
39
Describe the presentation of rotavirus infection.
- 2 day incubation period
| - 7 days of osmotic diuresis with vomiting, fever, headache, and abdominal pain
40
How is rotavirus diagnosed?
via EIA or latex agglutination of stool sample
41
Describe the pathogenesis of rotavirus.
produces NSP4, an enterotoxin, and causes lysis of epithelial cells
42
Describe the rotavirus vaccine.
produced by human/bovine reassortment and meant only to prevent severe disease, not all disease
43
Rotavirus
- a family of segmented, dsRNA GI viruses
- triple layer capsid with VP6, VP4, VP7
- major cause of infantile diarrhea
- most common in those 6-24 months old in the cooler months
- 2 day incubation period followed by 7 days osmotic diuresis, vomiting, abdominal pain
- diagnosed via EIA or latex agglutination of stool sample
- vaccine available is only meant to limit severity
- pathogenesis relies on NSP4 enterotoxin and cell lysis- most common is group A G1P[8]
44
The first ever retrovirus identified was what?
Human T-cell Leukemia Virus 1
45
HTLV-1 infects what population of host cells?
CD4 T Cells
46
HTLV-1 is known to cause what diseases?
- asymptomatic infection in 95% of cases
- infection in early life results in adult T cell leukemia/lymphoma
- tropical spastic paraparesis
- HTLV-1 associated myelopathy
47
Where does HTLV-1 have a particularly high prevalence?
Japan
48
How is HTLV-1 primarily transmitted?
breast feeding
49
HTLV-1
- the first retrovirus discovered
- infects CD4 T cells
- transmitted via breast feeding but also sexually and via blood
- most infections are asymptomatic but may cause adult T-cell leukemia/lymphoma, tropical spastic paraparesis, or HTLV-1 associated myelopathy
50
Describe the genome of HIV-1.
a diploid RNA retrovirus with 3 major genes: env, pol, gag
51
HIV-1 targets which host cell population?
CD4 T cells and those of monocyte/macrophage lineage
52
How does HIV-1 enter target cells?
gp41 and gp120 interact with host CD4 TCR and CCR5 or CXCR4 co-receptors
53
How is HIV-1 transmitted?
via blood, intercourse, and perinatally
54
Describe an acute HIV-1 infection.
headache, myalgia, swollen lymph nodes, CNS findings, pneumonitis, and diarrhea lasting weeks
55
Why does HIV-1 often cause diarrhea during acute infection?
because it has a tropism for GALT
56
What happens to CD4, CD8, and p24 levels during acute HIV-1 infection?
- CD4 levels drop
- CD8 levels rise
- p24 antigen levels rise in the blood
57
What is the average time between acute HIV-1 infection and AIDS onset?
ten years
58
What defines AIDS?
- a CD4 count below 200 cells/uL
| - or an AIDS defining illness
59
Mycobacterial Disease
- a reactivation of M.tb or M. avium complex in HIV patients
- M.tb associated with pneumonia
- MAC associated with disseminated disease in HIV patients
60
How does P. jiroveci related to HIV patients?
- all HIV patients given TMP-SMX as prophylaxis
| - causes a severe pneumonia
61
The most common fungal infection in HIV patients is what?
candidiasis
62
How does candidiasis present?
white plaques with a "stuck on" appearance found on the tongue, palate, esophagus, or vagina of immunocompromised patients
63
Hairy Leukoplakia
a disease caused by EBV in AIDS patients and generates a large white patch on the tongue
64
Taxoplasmosis
an opportunistic infection acquired from undercooked meat or cat feces that causes CNS disease in HIV patients
65
Describe the presentation of taxoplasmosis.
- a CNS disease
- headache, confusion, weakness, and fever
- MRI reveals a ring enhancing lesion
66
Ring enhancing lesions on MRI are characteristic of what illness?
taxoplasmosis infection
67
Cryptococal Meningioencephalitis
- a cryptococcus neoformans infection common in those with a CD4 count below 100 cells/uL
- presents with subacute fever, malaise, headache, stiff neck, and photophobia
- diagnose with CSF analysis and culture
68
What organism causes cryptococcal meningoencephalitis?
cryptococcus neoformans
69
How is cryptococcal meningoencephalitis diagnosed?
CSF analysis and culture
70
Who is cryptococcal meningoencephalitis most likely to affect?
those with a CD4 count below 100 cells/uL
71
How do we define AIDS-related dementia complex?
a score of more than 2 SD below mean within two cognitive domains along with ADL impairment
72
What 5 gross and histologic findings are consistent with AIDS-related dementia complex?
- white mater pallor
- microglial nodules
- multinucleated giant cells
- perivascular infiltrate
- frontal and temporal lobe neuron loss
73
Describe the genome of herpesviridae viruses.
- a family of dsDNA viruses
- genome has an L and S region, each bordered by inverted repeats
- transcription is temporal with alpha, beta, and gamma genes encoding transcription regulators, DNA replicators, and structural components, respectively
74
All herpes viruses are capable of what?
latency
75
Herpesviridae
- a family of dsDNA viruses that utilize temporal transcription
- three subfamilies include alpha, beta, and gamma
- capable of forming syncytia
- enter cells via fusion, capsids forming nucleus and leave via double envelopment process, causes cell lysis
76
Describe the herpesviridae life cycle.
- enter via fusion event
- transcription of genome via host RNA pol II in nucleus
- capsid assembles in the nucleus
- capsid leaves via a double envelopment proccess
- acquires an envelop from the golgi
- leaves the cell via lysis
77
How are HSV-1 and HSV-2 primarily spread?
- HSV-1 via oral contact and saliva
| - HSV-2 via sexual contact or autoinoculation
78
HSV-1
- a dsDNA virus of the alpha herpesviridae subfamily
- spread primarily via saliva
- infects mucoepithelial cells
- remains latent in trigeminal ganglia or DRG and reactivated by stress, light, immunosuppressants
- typically cause oral lesions but also cause encephalitis, keratoconjunctivitis, herpes whitlow, and herpes gladitorium
79
Where does HSV-1 typically remain latent?
the trigeminal ganglia or DRG
80
HSV-1 causes what diseases?
- primarily herpes labials (cold sore)
| - also encephalitis, keratoconjunctivitis, herpes whitlow, and herpes gladitorum
81
Describe the presentation of a cold sore.
- pain, tingling, and itching followed by the appearance of erythema and edema
- papule and vesicles form within 24 hours
- ulcerates and heals 7-10 days later
82
HSV-2
- a dsDNA virus of the alpha herpesviridae subfamily
- primarily spread via sexual contact
- usually found latent in sacral ganglia
- most commonly causes genital lesions
- also causes encephalitis, pharyngitis, herpes whitlow, and neonatal herpes
83
Where does HSV-2 usually reside latent?
sacral ganglia
84
What diseases does HSV-2 cause?
- usually genital lesions
| - also encephalitis, pharyngitis, herpes whitlow, and neonatal herpes
85
Describe an acute genital herpes infection.
- incubation period of 5 days
- tender lymph nodes, fever, dysuria, itching
- followed by lesions
- resolves 3-4 weeks later with recurrences being shorter
86
Eczema Herpeticum
a herpes infection of children with pre-existing atopic dermatitis and burn patients which spreads cutaneous
87
Herpes Whitlow
an infection of the hands and wrists from body fluids or open sores infected by either HSV-1 or HSV-2
88
Herpes Gladitorum
a superficial skin lesion caused by HSV-1, most commonly on the feet of wrestlers
89
Herpes Keratoconjunctivitis
a monocular conjunctival infection by HSV-1 that my cause corneal damage and blindness with recurrent infection
90
What is the most common cause of sporadic encephalitis?
herpes infection
91
Herpes encephalitis affects which brain regions most?
temporal and inferior frontal lobes
92
How does herpes encephalitis present?
with fever, confusion, seizures, and coma
93
What is the significance of Cowdry Type A inclusion bodies?
they are herpes inclusion bodies present in the histology of herpes encephalitis
94
Neonatal Herpes
- a usually fatal infection by HSV-2 acquired in utero, usually during a primary infection of the mother
- spreads to liver, lungs, and CNS because the immune system isn't fully developed
- causes brain atrophy
95
Which organs are most affected by neonatal herpes?
liver, lungs, and CNS
96
Describe the gross pathology of neonatal herpes.
- brain atrophy
| - disseminated yellowish necrotic liver lesions
97
What is the peak incidence of Varicella-Zoster virus infection?
age 2-6
98
Describe the spread of VZV in humans.
- transmitted via droplets to the respiratory tract
- carried by lymphatics to the blood
- then onto the skin and mucous membranes
99
Where does VZV typically remain latent?
sensory ganglia
100
What kind of vaccine is the VZV vaccine?
a live, attenuated vaccine
101
What is zostavax?
a zoster vaccine given to those over the age of 60
102
Describe congenital varicella?
a varicella infection acquired in utero that causes scaring of skin, limb hypoplasia, and CNS defects
103
EBV
- a gammaherpes virus spread via saliva
- targets B cells
- three outcomes: active infection, latent infection, immortalization and cancer
- has four latency programs depending on the expression profile of nine genes, each program causes a different set of diseases
104
What are Downey cells?
abnormally activated lymphocytes associated with EBV infection and transformation of B cells
105
How is EBV spread?
via saliva
106
What are the three outcomes associated with an EBV infection?
- active infection
- latent infection
- stimulation and immortalization of B cells to cause cancer
107
EBV targets what human cell population?
B cells
108
How does EBV cause lymphoma/leukemia?
its 9 latency genes interfere with cellular control and differentiation of B cells
109
What causes infectious mononucleosis?
EBV infection
110
Heterophil antibodies are associated with what illness?
EBV infection
111
Describe the presentation of infectious mono.
- cervical lymphadenopathy
- splenomegaly
- exudative pharyngitis
- hepatomegaly
- presence of heterophil antibodies and downey cells
112
What are the complications of infectious mono.
- CNS complications
- ruptured spleen
- laryngeal obstruction
113
The severity of mono correlates with what?
the age of infection with younger being associated with milder illness
114
Burkitt's Lymphoma
- a cancer of the lymphatic system
- comes in three types: endemic, sporadic, and HIV-1 associated
- all forms associated with a translocation of chromosome 8 in the region of c-myc and chromosome 14 or 22
115
What is unique about endemic Burkitt's lymphoma?
- associated with EBV infection
| - usually seen in those 2-14 living in equatorial Affrica
116
What is the most common form of Burkitt's lymphoma in the US?
sporadic
117
What tumor types are endemic, sporadic, and HIV-1-associated Burkitt's lymphoma associated with?
- endemic: extra nodal tumors
| - sporadic and HIV-1: lymph node tumors
118
Burkitt's lymphoma is associated with what genetic factor?
a translocation of chromosome 8 around the region of c-myc with either chromosome 14 or 22
119
EBV is associated with which lymphomas and leukemias?
- Hodgkins lymphoma
- hairy oral leukoplakia
- African Burkitt's lymphoma
120
What is Hodgkin's lymphoma? Which age group is most affected?
- a rare lymphoma in the US associated with EBV
| - affects those 16-34 and those over 55
121
What are Reed-Stenberg cells?
cells associated with Hodgkin's lymphoma that have a B cell origin
122
What is the most common virus transmitted to fetuses?
CMV
123
CMV causes what illnesses in those that are immunocompetent?
asymptomatic infection or infectious mono
124
Infectious mono is associated with what infections?
EBV and CMV
125
What is the most common infection in solid organ transplant recipients?
CMV
126
CMV is the leading infection in what three categories?
- virus transmitted to fetus
- post-transplant infection
- leading infection and cause of bone marrow transplant failure
127
What are the outcomes of a CMV infection?
- immunocompetent: asymptomatic or mon
- baby of seronegative mother: CMV inclusion disease
- immunocompromised: multisite disease with retinitis, encephalitis, colitis, and pneumonia
128
Describe post-transplant CMV infection.
- presents 1-3 months post-transplant
| - with fever, pneumonitis, GI complaints, hepatitis, and poor graft function
129
What sort of infection will lead to CMV inclusion disease?
CMV infection of a fetus in a seronegative mother
130
What are the two leading causes of mental handicap at birth?
1) Down's syndrome
| 2) congenital CMV infection
131
How do we define congenital CMV?
presence of CMV in saliva or urine within 3 weeks of birth
132
CMV inclusion disease
- a multisystem CMV disease
- temporary liver problems, jaundice, spleen problems, purple skin blotches, lung problems, and seizures
- along with permanent sensorineural hearing loss, vision loss, mental disability, microcephaly, ataxia
133
Describe the histology of CMV inclusion disease
- enlarged cells with intranuclear inclusion
- surrounded by a halo with buckshot appearance
- margination of chromatin
134
What organism is roseola infantum associated with?
HHV-6
135
Describe the presentation of roseola infantum.
- 6m to 3y old
- abrupt onset high fever lasting three days (possibly with febrile seizures)
- rapid cessation of fever and onset of mild, pink, morbiliform exanthema lasting 1-2 days
136
Where is Karoposi Sarcoma Herpesvirus common?
Eastern Europe and North America
137
Which herpes virus is not ubiquitous like the rest?
Karposi Sarcoma Herpesvirus
138
Kaposi sarcoma herpesvirus has a high prevalence in which populations?
- older men of Italian or Jewish ancestry
| - homosexuals
139
What are the four forms of Kaposi sarcoma?
- classical
- African aggressive
- transplantation associated
- AIDS-associated
140
Describe African aggressive Kaposi sarcoma.
- seen in East and Central Africa
- nodular, infiltrative, lympho-adenopathy
- rapidly fatal and without treatment
141
How does Kaposi sarcoma present?
purple skin blotches on the skin with GI involvement
142
To which subfamily does Kaposi sarcoma belong?
gammaherpesviridae
143
Describe the genome of the influenza viruses.
segmented, negative strand RNA viruses
144
Describe the duration of the incubation period and symptomatic period of most influence viruses.
- 1 to 4 day incubation period
| - 2 to 5 day symptomatic period
145
How do most influenza viruses spread?
large droplets, aerosol, or fomites
146
When are influenza viral particles spread during the course of an infection?
one day before symptoms and for up to six days
147
Which proteins are important for the infectivity of the influenza viruses?
- hemaglutinin
- neuraminidase
- M2
148
What mediates the pathogenesis of influenza A virus?
a cytokine storm
149
What are three pulmonary and three non-pulmonary complications of influenza A?
- pulmonary: pneumonia, croup, exacerbation of COPD
| - non-pulmonary: myositis, toxic shock syndrome, Guillan-Barre syndrome
150
Influenza A
- a segmented, negative strand RNA virus
- pathogenesis is mediated by cytokine storm
- causes influenze syndrome and pneumonia
- complications include pneumonia, croup, COPD exacerbation, toxic shock, Guillan-Barre
- vaccinations are lifelong but subtype specific
151
Describe the presentation of influenza A.
- 3 days of systemic symptoms
| - plus dry cough,, pharyngeal pain, and nasal congestion
152
Paramyxoviruses
- a family of segmented, negative strand RNA viruses
- includes measles, mumps, respiratory syncytial virus, and human metapneumovirus
- share a fusion F protein implicated in syncytial formation
- begin with inoculation of the respiratory tract and spread
- cell-mediated immunity is important to control and pathology
153
Measles belong to which family of viruses?
paramyxoviridae
154
Describe the incubation period and symptomatic presentation of measles.
- 10-14 day incubation
- develop the three Cs: cough, coryza, conjunctivitis
- additional symptoms are temperature and a rash that begins on face/head and persists 5-6 days
155
Measles
- a paramyxovirus with segmented, negative strand RNA
- 10-14 day incubation period followed by the three Cs (cough, coryza, conjunctivitis), temperature, and rash that persists 5-6 days
- cell-mediated immune system is vital to control and meditates pathology
- most common complication is acute otitis media
- may be followed decades later by subacute sclerosing panencephalitis
156
Measles targets which host cell population?
cells of the respiratory tract
157
What is subacute sclerosing panencephalitis?
a disease that follows measles by 1-10 years and is characterized by cognitive and then motor dysfunction with death coming in 6 months after symptom onset
158
The paramyxoviruses begin by inoculating what tissue?
respiratory tract
159
Describe the presentation of mumps.
- viral parotitis and swelling
- can cause encephalitis or orchitis
- may lead to juvenile diabetes if it affects the pancreas
160
When is respiratory syncytial virus most common?
in the winter
161
Respiratory syncytial virus is the most common cause of what diseases in infants?
- bronchiolitis
- LRTI
- pneumonia
162
Who is most at risk for respiratory syncytial virus infection?
infants with congenital heart disease, bronchopulmonary dysplasia, or congenital immune deficiency
163
How does respiratory syncytial virus present?
- fever, chills, wheezing, shortness of breath
| - cough, congestion, coryza, rhinorrhea, conjunctivitis, apnea
164
How is respiratory syncytial virus treated?
with supportive care, ribavirin, and monoclonal antibodies
165
Human Metapneumovirus
- similar presentation and treatment as respiratory syncytial virus
- causes LRTI and URTI in children
166
Parainfluenza Virus
a paramyxovirus with immune-mediated pathology that includes croup, bronchiolitis, and pneumonia in stem cell and organ transplant patients
167
Rubella
- a positive strand RNA virus that infects the respiratory tract
- presents with fever, sore throat, lymphadenopathy and a characteristic rash lasting up to five days that is less severe than measles
- causes arthralgia and arthritis in adults
- can be passed during first trimester to cause congenital rubella
- pathology is partially antibody mediated
168
When are rubella outbreaks common in the US?
in college
169
Describe the presentation of rubella.
- fever, sore throat, lymphadenopathy
- rash, less severe than measles, lasting five days
- may cause arthralgia and arthritis in adults
170
Under what circumstances does congenital rubella occur?
when mothers are infected during the first trimester
171
How does congenital rubella present?
- with a classic triad of cataracts, heart defects, and sensorineural deafness
- often have premature delivery and is fatal
172
To which family do the rhinoviruses belong?
picornaviridae
173
Describe the time course of rhinovirus infection.
- 2 day incubation period
| - 9-10 days symptomatic
174
How is rhinovirus spread?
via aerosol and fomites
175
What are the symptoms of rhinovirus?
- self-limiting URTI
| - cough, headache, sore throat
176
Describe the time course of coronaviruses.
- 3 day incubation
| - 6-7 days symptomatic
177
The leading cause of the common cold is what?
rhinovirus
178
Coronavirus is known to cause which disease other than the common cold?
- SARS
| - MERS-CoV
179
How do coronaviruses compare to rhinoviruses?
- have a longer incubation period and shorter symptomatic period
- coronavirus peaks in winter/early spring while rhinovirus peaks in summer/fall
180
When does coronavirus incidence peak?
summer/fall
181
When does rhinovirus incidence peak?
winter/early spring
182
What is SARS?
- a coronavirus disease typically acquired during travel that presents with fever, headache, myalgia and progresses to a LRT period 3-7 days later with a dry, unproductive cough
- hasn't been seen since 2004
183
MERS-CoV
- a coronavirus disease endemic to the middle east
| - believed to be related to camels
184
Describe the polyomaviruses.
- a dsDNA subfamily of the papovaviridae family
- includes JC, BK, and SV-40
- productive infection leads to cell death but non-productive infection leads to cancerous transformation
- invade via the respiratory tract but replicate in kidney cells
185
Describe polyomaviridae virions.
- dsDNA genome complexed with histones
- genome has a control region separating bidirectional early and late genes
- transcription controlled by Large T antigen
186
What is the significance of the Large T antigen?
it is a transcriptional regulator for polyomaviruses that is also implicated in ongenesis
187
JC virus targets which host cell population?
oligodendrocytes
188
JC virus enters the host via the ___ but persists in what two places?
- enters via respiratory tract
| - persists in B cells and the kidney
189
Describe the presentation of JC virus.
- impaired speech and vision
- mental deterioration
- paralysis
- sensory abnormalities
- death within 3-6 months
190
PML is caused by what pathogen?
JC virus
191
Areas of irregular granularity in white matter are a feature of which disease?
JC virus/PML
192
BK viruses causes what disease?
polyomavirus associated nephropathy
193
BK virus is linked to which cancers?
- beta-islet adenomas of the pancreas
| - brain tumors
194
What is the most important infectious complication affecting kidney transplant patients?
BK virus/polyomavirus associated nephropathy
195
BK virus affects which renal cells?
epithelial cells of the tubules and collecting ducts
196
Where did most human SV-40 infections originate?
contaminated polio vaccine preparations grown in rhesus kidney cells
197
SV-40 has been linked to which cancers?
osteosarcomas, mesotheliomas, meningiomas
198
Which papillomavirus are most risky?
16 and 18
199
Which papillomaviruses are low risk mucosal types?
6 and 11
200
Which viruses causes warts?
papillomaviruses
201
What is the significance of late and early genes in papillomaviruses?
- early genes are sufficient for cancerous transformation
| - late genes expressed in a productive infection
202
Papillomaviruses belong to what family?
papovaviridae
203
Papillomaviruses infect what cell type?
basal cells of surface squamous epithelium
204
How does papillomavirus present in immunocompromised patients?
they are often covered with large warts
205
Which papillomavirus genes are oncogenic?
E6 and E7 inhibit p53 and Rb
206
Name the two parvoviruses.
B19 and the defective adeno-associated virus
207
Parvoviruses only replicate in what cells?
those in the S phase
208
Describe the genome of parvoviruses.
- ssDNA with inverted repeats that form hairpins
| - these hairpins allow the genome to self-prime
209
What happens to the positive and negative strands of parvovirus DNA?
they are packaged into separate virions
210
Adeno-associated virus requires co-infection with one of which two viruses?
- adeovirus
| - herpesvirus
211
How does the adeno-associated virus establish a latent infection?
it integrates its genome into the human chromosome 19 via homologous recombination
212
Describe the appearance of adenovirus.
icosahedral with fibers extending from the apexes
213
Adenovirus causes what important illness for which there is a vaccine?
adult respiratory distress syndrome in military recruits and boarding schools
214
Slapped cheek rash is characteristic of what infection?
B19 parvovirus
215
What are the significant complications of B19 disease?
- aplastic crisis
- anemia
- hydros fetalis
216
B19 virus replicates in which cell types?
URT epithelial cells and erythroid precursor cells
217
B19 will cause aplastic crisis in which patients?
those with hemolytic anemia
218
What accounts for the biphasic nature of B19-related illnesses?
- the first phase is related to viremia
| - the second to B19-antibody complexes
219
Why should patients with a B19 infection not be given IVIG?
because part of the pathology is mediated by B19-antibody complexes
220
How does B19 infection present in young patients?
- prodrome of fever, sore throat, malaise
| - followed by slapped cheek rash
221
How does B19 infection present in adults?
with long lasting joint pains and arthritis
222
Which group of dsDNA viruses replicate in the cytoplasm?
poxviruses
223
What poxvirus causes small pox?
variola
224
Name a four poxviruses.
- variola
- vaccinia
- orf
- molluscum contagiosum
225
Describe the presentation of small pox.
- abrupt onset fever
- appearance of a macular rash on day 3
- rash progresses to vesicles
226
What are alphaviruses?
- a genus of arboviruses with postive-strand RNA viruses lacking a poly(a) tail
- transmitted by mosquito vectors so disease is more common in the summer
- humans are typically a dead end host
227
Name the important flaviviruses.
- dengue fever virus
- yellow fever virus
- west nile virus
- hepatitis C
228
Where do flaviviruses replicate?
the salivary glands of mosquitos
229
Flaviviruses cause which group of diseases?
hemorrhagic fevers
230
Describe the transmission cycle of dengue fever virus.
human-vector-human
231
Dengue fever virus causes what two diseases?
- hemorrhages fever
| - dengue shock syndrome
232
Describe the three phases of dengue fever.
- febrile phase: sudden fevere with orbital headache, myalgia, and a measles-like rash with petechiae
- critical phase with plasma leakage, liver dysfunction, and shock
- recovery characterized by intense itching and a slowed heart rate
233
How do most dengue fever viral infections conclude?
resolution after the febrile phase
234
What are the risk factors for severe dengue fever viral infection?
- virus strain
- host genetics
- age
- multiple circulating serotypes
235
Where is yellow fever endemic?
South America and sub-saharan Africa
236
Describe the transmission cycle of yellow fever.
monkey-mosquito-human or human-mosquito-human
237
How does yellow fever present?
- chills, fever, headache, GI upset
- Paget's sign (bradycardia) after 3-4 days
- jaundice, hemorrhagic signs
238
Describe the transmission cycle of west nile virus.
bird reservoir-mosquito-human
239
How do most arboviruses survive the winter?
in dormant female mosquitos and eggs
240
What disease is west nile virus known to produce?
- west nile fever
| - west nile neurologic disease
241
What is west nile neurologic disease?
- meningitis
- encephalitis
- polio-like flaccid paralysis
242
Zika virus causes what symptoms?
- Guillan-Barre
- microencephaly
- paralysis
- non purulent conjunctivitis
- facial exanthema
- exanthema on trunk
243
Where is Zika virus most prominent?
in Brazil
244
Which group of viruses is known to cause cancer when they lead to an unproductive infection?
the popavaviridae family of viruses (polyomaviruses and papillomaviruses)
245
What do the bunyaviridae viruses have in common?
they depend on wild animals (mainly rats) for persistence
246
The hantaviruses are perpetuated by what non-human animal?
rodents
247
What is the most clinically relevant hantavirus subtype?
the sin nombre subtype
248
Why is the sin nombre hantavirus so clinically important?
- it is found in north America
- carried by deer and mice
- causes a pulmonary syndrome with 50% mortality
249
The hantaviruses cause what diseases?
- sin nombre subtype causes a pulmonary syndrome
| - the other forms cause renal pathology and aren't as fatal
250
Which types of hantaviruses are less fatal?
the ones other than sin nombre which cause renal pathology rather than the pulmonary syndrome
251
How is hantavirus treated?
ribavirin early in the disease course
252
What is Hantaan disease?
- a multi system disease caused by the hangman subtype of hantavirus
- endothelial damage leads to vasodilation and congestion with hemorrhages
- death can occur in the hypotensive or oliguric phase of the illness
253
How does Hantaan disease present?
- febrile phase is a severe flu-like illness and rash
- hypotensive phase begins at day 5
- oliguric phase begins at day 9 with renal failure and shock
- diuretic phase spans day 12-14
- convalescence may require up to four months
254
What is Hantaan pulmonary syndrome?
a form of Hantaan disease in which the endothelial damage is concentrated in the lungs, causing shock and cardia complications
255
Name the two important phleboviruses.
- rift valley fever
| - sandfly fever
256
Describe the presentation and time course of sandfly fever.
- not seen in the US
| - a 2-6 day incubation period is followed by rapid onset, high fever and malaise for 2-4 days
257
What animal perpetuates rift valley fever virus?
sheep
258
What is important to remember about rift valley fever?
- perpetuated by sheep and found primarily in Africa
- peak incidence follows rainfall
- 2-6 day incubation period is followed by 2-5 days of flu-like symptoms
259
Which genus of virus has captured ribosomes from host cells?
the arenaviridae family (lassa fever virus)
260
How are arena viruses spread?
contact with rodent urine or saliva
261
What is the mortality associated with arena viruses?
15-30 percent
262
Where is lassa fever endemic?
West Africa
263
How is Lassa Fever Virus spread to humans?
contact with rodent urine or feces and some human-to-human transmission
264
What separates Lassa Fever virus from the other arenaviruses?
there is some degree of human-to-human transmission
265
How are most bunyaviruses treated?
with ribavirin early in the disease course
266
List the important bunyavirus genera.
- hantaviruses
- phleboviruses
- arenaviruses
267
List the important poxvirus genera.
alphaviruses and flaviviruses
268
Describe the presentation of Lassa fever.
- 3-5 day incubation period with insidious onset
- ulcerative pharyngeal lesions
- possible pneumonia, myocarditis, shock
- hemorrhagic fever
- sensorineural deficits during convalescence
269
What is important to remember about the convalescent period of Lassa fever?
it may involve sensorineural deficits that are unrelated to severity of the disease and may persist for life
270
Describe the structure of rhabdoviruses.
- bullet shaped viruses
- five structural proteins
- helical nucleocapsid
- negative RNA viruses
271
How does rabies virus bind host cells?
antigenic site III on the G protein
272
Negri bodies are a feature of what infection?
rabies virus
273
What are negri bodies filled with?
coiled ribonucleoprotein
274
Rabies virus infects what organ?
the CNS
275
Why is rabies vaccination unique?
it is one of few that allows for post-exposure vaccination to prevent disease onset
276
What mortality is associated with rabies virus?
nearly 100% once symptoms appear
277
Describe the pathogenesis of rabies virus.
1) inoculation
2) replication in muscle
3) enter PNS
4) replication in DRG
5) ascend spinal cord
6) complete CNS infiltration
7) descending infection via nervous system to eye, salivary glands, skin, pancreas, etc.
278
How does rabies virus neuronal transport compare to that of herpesviruses?
rabies virus is carried via retrograde transport in motor neurons whereas herpes is carried via retrograde and anterograde transport in sensory afferents
279
The incubation period of rabies depends on what four factors?
- concentration of virus introduced
- proximity of wound to the brain
- severity of the wound
- host's immune status
280
What is a typical incubation period for rabies?
2-12 weeks but ranging from 4 days to 1 year
281
Describe the presentation of classical rabies.
- a prodromal phase of fever, headache, fatigue, anorexia lasting 2-10 days
- neurologic phase of hyperactivity, disorientation, hallucinations, hydrophobia (don't want to eat or drink) lasting 2-7 days
- coma/paralysis with continued mental deterioration leading to sudden cardiac or respiratory arrest
282
What is the most classic feature of rabies disease?
"hydrophobia" - don't want to drink or eat
283
What is dumb rabies?
a variant of rabies disease in which patients skip the neurologic phase and go straight from prodrome to paralysis
284
Why is the G protein important to the rabies virus?
important for entry into host cells and for pathogenesis
285
What are pathogenic and non-pathogenic rabies virus?
- pathogenic has an arginine at position 333 of the G protein
- glutamine or isoleucine in the non-pathogenic variants
286
How does non-pathogenic rabies differ in presentation from pathogenic?
- slower entry into cells
| - slower spread
287
What is the most important type of immunity for rabies virus?
humoral immunity focused on anti-G protein antibodies
288
Why does post-exposure vaccination to rabies work?
because of the long incubation period of the virus
289
Which animals are most likely to carry rabies?
- raccoons
- skunks
- bats
- foxes
290
How is rabies virus diagnosed?
RT-PCR
291
What samples are collected to perform RT-PCR for rabies?
saliva and skin (which are fed by descending infection from the CNS)
292
How are patients treated after suspected exposure?
- wound debridement
- passive immunization with human rabies Ig or equine rabies Ig
- active immunization
293
What kind of virus is the rabies vaccine?
inactivate whole virus
294
Name the two rabies vaccines currently available.
- IM human diploid cell vaccine
| - IM purified chick embryo vaccine
295
Describe the Filoviruses.
- long and skinny but pleomorphic in shape
| - polyploidy, negative strand RNA with 1-20 copies per virion
296
List the important filovirus structural proteins.
- nucleoprotein, VP30, VP35, and polymerase L are associated with replication and transcription
- glycoprotein, vision proteins VP24 and VP40 are membrane-associated
297
What is filovirus sGP?
soluble glycoprotein believed to be a truncated envelop from unedited RNA and secreted by the virus
298
What are VP40 and VP24 in the context of filoviruses?
they are matrix proteins
299
The most clinically important filovirus is what?
ebolavirus
300
How is ebola virus transmitted?
direct contact with body fluids, fomites, or infected animals
301
Describe ebola hemorrhagic fever.
- incubation period of 3-21 days
- initial symptoms are non-specific
- followed by development of an erythematous, maculopapular rash
- hemorrhages begin appearing at the conjunctiva, mucosal membranes of oral cavity, and GI tract skin
- red eyes are a common feature as is bleeding from orifices
302
Describe the timecourse of ebola hemorrhagic fever.
- 3-21 day incubation period
| - 7-14 days until death
303
Death due to ebola is typically due to what?
blood loss and shock
304
What role do ebola virus proteins play in the pathogenesis of ebola hemorrhagic fever?
- GP forms virus like particles and causes cell death and endothelial activation
- sGP has anti-inflammatory properties (particularly against TNFa)
- VP24 and VP35 are type I interferon antagonists
305
Name two histologic findings associated with ebola virus.
- eosinophilic inclusions in hepatocytes
| - antigen in skin tissue
306
How does ebola reach humans from bats?
via ecological "spillover dynamics"
307
How is ebola hemorrhagic fever treated?
- ribavirin early
- supportive care including blood and clotting factor replacement
- monoclonal antibodies against the virus envelop glycoprotein
