DNA Viruses Flashcards
where do DNA and RNA viruses replicate, respectively?
DNA viruses replicate in nucleus (except Poxvirus)
RNA viruses replicate in cytoplasm
what virus does this describe?
- smallest pathogenic virus
- has linear (-)ssDNA
- replicates only in dividing cells, esp. erythrocyte precursors in the bone marrow
Parvovirus B-19!
common childhood infection with fever/rash (“slapped cheek”) or transient anemia (aplastic crisis!)
what kind of virus is Parvovirus B-19 and what kind of disease does it cause? (3)
Parvovirus B-19: linear (-)ssDNA
clinical:
1. Fifth disease: common childhood infection with fever and “slapped cheek” rash + trunk/extremities
2. aplastic crisis (patients with hematological abnormalities)
3. 1st trimester spontaneous abortions/birth defects
what kind of viruses are Papovaviruses and where did this name come from?
Papovaviruses: dsDNA viruses (require host cell replication machinery), named for its 3 original members:
- PApilloma - epithelial lesions
- POlyoma - tumor in animals, subclinical in humans
- Simian VAcuolating virus 40 - no human disease
where does Human Papilloma Virus (HPV) replicate, and on what terms?
HPV replicates in epithelial cells, but cells must differentiate for virus to go through full replication cycle -
therefore, virus early proteins keep infected cell in division cycle (ultimately kills cells)
*remember that HPV is Papovavirus, dsDNA genome
what disease does HPV most commonly cause? what is it a risk factor for?
most commonly causes condylomata (warts) - proliferative lesions
major risk factor for cervical cancer (sexual transmission)
what 2 viral proteins does HPV use to disrupt host cell cycle, and how do they work?
early viral proteins E6 and E7
E6: binds p53 (blocks apoptosis)
E7: binds Rb (Retinoblastoma) to disinhibit E2F (transcription factor)
how does HPV function as a major risk factor for cervical cancer? (how does malignancy occur?)
abortive HPV infection —> viral DNA fragment integrated into host DNA —> early genes expression
early gene expression drives cell into continuous division, but late proteins are not made so cells are not killed
what type of virus does this describe?
- transforms cell cultures but does not cause human cancers
- E1A and E1B drive infected cells into division
- 40+ types but only a few cause infection - respiratory, conjunctivitis, GI, febrile pharyngitis
Adenovirus
what family of virus does this describe?
- largest, most complex
- replicates in cytoplasm
- enveloped, brick-shaped
- lateral bodies contain proteins that modulate immune responses
Poxvirus: DNA virus but replicates in cytoplasm because it makes its own replication enzymes
which DNA virus replicates in the cytoplasm?
Poxvirus: largest and most complex, enveloped, brick-shaped
you identify a large brick-shaped, enveloped virus that contains lateral bodies - what virus is this, and what do the lateral bodies contain?
Poxvirus: largest, most complex, DNA virus but replicates in cytoplasm
lateral bodies contain proteins that modulate immune responses
what 3 Poxvirus are pathogenic to humans? (DNA virus)
- Smallpox
- Molluscum contagiosum virus: local infection (chest, face) of fleshy bumps (dome with little indentations/umbilications)
- Monkey pox
Pt is an 8yo M presenting with fleshy, dome-shaped bumps covering his chest, which began 3mo ago. Microscopy of one of the lesions reveals large, brick-shaped viruses within cytoplasm.
What is going on?
Molluscum contagiosum virus: type of Poxvirus (DNA virus), causes local (face, chest, back) infection of fleshy bumps with indentations (umbilications)
can last months, self-limiting
What are the 2 clinical forms of Smallpox (type of Poxvirus, DNA virus)?
- Variola major: severe, most common - extensive rash, high fever
- Variola minor: less common, less severe
*note epidemics were once widespread, but has since been “eradicated” - vaccination no longer performed, potential for bio-warfare
describe the transmission and pathology of Smallpox (DNA virus, Poxvirus)
Smallpox: transmission via respiratory droplets or fomites, infects macrophages
rash (oral cavity and body): macules —> papules —> vesicles —> pustules —> scab —> pox (scar)
recovery = lifelong immunity
how is Monkeypox (Poxvirus, DNA virus) transmitted, and what disease does it cause?
Monkeypox: transmitted via MSM and household contacts (via direct contact, respiratory secretions, fomites, vertical)
—> systemic febrile illness, rash (similar to smallpox but fewer), possible complications in immunocompromised
what type of vaccine is available for monkeypox (DNA poxvirus)?
live, attenuated vaccinia virus (also works for smallpox)
*remember that Vaccinia virus is the vaccine strain of smallpox, but smallpox vaccine is not given routinely anymore because it is “eradicated”
for the following forms of Human Herpesvirus, name what disease it causes:
a. HSV1
b. HSV2
c. Varicella-Zoster
d. Epstein-Barr
a. HSV1: cold sores
b. HSV2: genital herpes
c. Varicella-Zoster: Varicella = chickenpox, Zoster = shingles (but same virus)
d. Epstein-Barr: infectious mononucleosis
what kind of virus and shape is Human Herpesvirus?
enveloped linear dsDNA, icosahedral capsid
[recall that because it is enveloped, fusion occurs at host plasma membrane, leaving spike glycoproteins on surface, which can serve as red flags for immune system]
what is contained in the tegument of Human Herpesvirus (linear dsDNA virus)?
tegument: amorphous shape, contains viral proteins and mRNA
describe the protein synthesis cascade of Human Herpesvirus (linear dsDNA virus)
immediate early genes —> delayed early genes (trigger DNA replication) —> late genes (structural proteins)
how are Herpes viruses (linear dsDNA) classified? name the strains in each category
alpha: HSV1, HSV2, VZV
beta: CMV, HHV6, HHV7
gamma: EBV, HHV8
contrast the general features of alpha to beta to gamma herpes (linear dsDNA)
alpha: large host range, short reproductive cycle, spread rapidly, latent in sensory ganglia, kill infected cells (HSV1, HSV2, VZV)
beta: restricted host range, long reproductive cycle, slow infectivity, latent in monocytes, infected cells become large (CMV, HHV6, HHV7)
gamma: specific to T/B lymphocytes, latent in lymph tissue (EBV, HHV8)
what category of herpes virus (linear dsDNA) does this describe?
large host range, short reproductive cycle, spread rapidly, latent in sensory ganglia, kill infected cells
alpha: HSV1, HSV2, VZV
what category of herpes virus (linear dsDNA) does this describe?
restricted host range, long reproductive cycle, slow infectivity, latent in monocytes, infected cells become large
beta: CMV, HHV6, HHV7
which category of herpes virus are restricted to infecting T and B lymphocytes?
gamma herpes: latent in lymph tissue (EBV, HHV8)
how does herpes virus (linear dsDNA) evade the immune system, allowing for its latency? (4)
- cytokine homologs bind receptors
- remove MHC I chains from ER or induce endocytosis of MHC I from cell surface (hides from NK cells)
- inhibit interferon activity
- block apoptosis
what 3 illnesses does HSV1 (alpha herpes) cause?
- herpetic gingivostomatitis
- herpetic keratoconjuntivitis
- HS encephalitis (usually immunocompromised)*
*usually herpes simplex virus is localized, rarely it invades CNS
which herpes strain causes the following diseases:
- herpetic gingivostomatitis
- herpetic keratoconjuntivitis
- HS encephalitis (usually immunocompromised)
HSV1 (alpha herpes)
what diseases (2) does HSV2 cause? (alpha herpes)
- genital herpes
- neonatal herpes
which strain of herpes causes genital and neonatal herpes?
HSV2 (alpha herpes)
how is herpes simplex virus (HSV1/2, alpha herpes) transmitted, and where does it establish latency?
HSV1/2: transmitted via contact of infected lesions
HSV1 - primarily oral/oral or oral/genital
HSV2 - primarily genital/genital
multiplies locally via mucous membranes, spreads along neurons (not systemic)
latent infection in 1 sensory nerve ganglion adjacent to site of infection
what would you see under a microscope if you examined a cell infected by herpes simplex virus (HSV1/2, alpha herpes)?
focal necrosis, multinuclear giant cells with intra-nuclear inclusion bodies (HSV is dsDNA virus, replicates in nucleus)
when can free virus be observed in HSV infection (alpha herpes)? what is the clinical relevance of this?
only see free HSV during initial infection - give human antisera as prophylaxis for high risk patients (small time window to catch free virus)
what is the major immune player against HSV infection (alpha herpes)?
Cytotoxic T lymphocytes (CTLs) - recognize viral glycoproteins on surface of infected cells
remember that herpes is enveloped and invades cell via fusion, so it will leave some evidence behind on the plasma membrane!
what is the function of latency-associated transcripts (LATs) of herpes virus (dsDNA)?
LATs: viral mRNA transcripts that keep herpes in latency - stops replication, avoids immune recognition
when stimulated by certain conditions (stress, UV light, etc), virus can travel back down latently-infected sensory neuron and infect epithelial/mucosal cells at same site as initial infection
how does Varicella-Zoster differ from HSV (both alpha herpes)?
VZV:
- transmitted via respiratory secretions (HSV: via contact)
- systemic (HSV: local)
- rash itches (HSV: painful lesions)
- latent in multiple sensory ganglion because it is systemic (HSV: only 1 sensory ganglion)
what kind of vaccine is available for Varicella-Zoster (alpha herpes)?
live attenuated vaccine
primary vs secondary viremia of Varicella-Zoster (alpha herpes)
primary viremia: lymph nodes and organs
secondary viremia: skin via WBC, rash in crops (waves) —> macules-papules-vesicles-pustules-scab-pox (scar)*
*note that this is the same sequence as smallpox, but chickenpox (VZV) occurs in waves - may see rashes at every stage in different parts of the body, while smallpox will be the same stage of rash throughout
how can you clinically differentiate between smallpox and chickenpox (VZV)?
both cause rashes that progress in this order: macules-papules-vesicles-pustules-scab-pox (scar)
however, chickenpox (VZV) occurs in crops (waves), so there will be rashes in different stages all over body, while smallpox rash will look uniform
describe how recurrence of VZV (alpha herpes) occurs and what clinically manifests
VZV: chickenpox first (Varicella), then shingles (Zoster) - but same virus
recurrence induced by immunosuppression —> virus travels along sensory axons (from latency) to sensory dermatomes
produces painful/vesicular lesions - usually one per episode (not all over body)
what kind of herpes does this describe?
- usually asymptomatic infection in children
- salivary gland disease of newborns (serious CNS disease) via breast-feeding of infected mother
- mononucleosis-like disease (lymphadenopathy, splenomegaly, etc)
Cytomegalovirus (beta herpes)
what kind of diseases does cytomegalovirus (beta herpes) cause?
- usually asymptomatic infection in children
- salivary gland disease of newborns (serious CNS disease) via breast-feeding of infected mother
- mononucleosis-like disease (lymphadenopathy, splenomegaly, etc)
choose the correct choice for cytomegalovirus (beta herpes):
slow vs fast infectious cycle
and
destruction vs no destruction of infected cells
CMV: slow infectious cycle, does not kill infected cells (no necrosis) —> cytomegaly with owl eyes (2 nuclei with nuclear inclusions)
what would you see under a microscope if you examined a cell infected by cytomegalovirus (beta herpes)?
it’s in the name - cytomegaly !
looks like owl eyes (2 nuclei with inclusions)
CMV does not kill infected cells and has slow infectious cycle
how is cytomegalovirus (CMV, beta herpes) transmitted, which cells does it infect, and how does it spread?
CMV: transmitted via infected body fluids (sexual, blood)
infects epithelial cells and leukocytes, spreads to all organs, latent in neutrophils and monocytes
how are HHV6 and HHV7 (beta herpes) transmitted, and what is their clinical significance?
HHV6/7: ubiquitous, transmitted via oral secretions, latent in peripheral blood lymphocytes, reactivated via pneumonitis/fever/hepatitis/encephalitis
HHV6 —> Roseola infantum (febrile, rash on trunk/neck), progression of HIV
HHV7 - asymptomatic
which herpes causes Roseola infantum and is also associated with the progression of HIV to AIDs?
HHV6 (beta herpes): ubiquitous, transmitted via oral secretions
Roseola infantum: febrile illness with rash on neck/trunk
which herpes virus is associated with several human tumors, including Burkitt’s, nasopharyngeal carcinoma, and Hodgkin’s? what illness does it definitely cause?
Epstein-Barr virus (gamma herpes) - causes infectious mononucleosis
[recall that EBV is associated with African Burkitt’s - lymphoma in jaw]
*recall that gamma herpes are latent in lymph tissues, which makes sense considering these associations
how is Epstein-Barr (gamma herpes) transmitted and where does it establish latency?
EBV: transmitted via respiratory secretions (saliva) with repeated exposure
infects and establishes latency in B cells (transfusions can then spread infected leukocytes)
carriers shed virus for life!
which herpes virus can cause infected cell proliferation, but has no cytopathic effects or inclusion bodies?
Epstein Barr (EBV): gamma herpes, infects B cells, associated with several cancers (African Burkitt’s, Hodgkin’s)
describe the host immune response to Epstein Barr (EBV, gamma herpes)
infected B cells produce nonspecific/polyclonal heterophile antibodies to viral membrane antigens
Downy cells: activated CD8 cells, “atypical lymphocytosis”, which kill infected B cells
*note that in immunosuppressed patients with ineffective cell-mediated immunity, lymphomas occur
with what herpes virus are Downy cells associated and what are they?
Epstein Barr (EBV, gamma herpes): infected B cells produce heterophile (polyclonal) antibodies against viral membrane antigens
Downy cells: reactive CD8 T cells kill infected B cells (“atypical lymphocytosis”)
how does EBV maintain latency in B cells of lymph tissue? (gamma herpes)
latent B cells express viral proteins (not antigenic for CTLs) necessary for latency maintenance
what test can be used to diagnose EBV (gamma herpes)?
EBV causes infectious mononucleosis
Paul-Bunnell Test (MonoSpot): detects heterophile antibodies, which agglutinate RBCs (polyclonal but specific to EBV)
[remember that heterophile Abs are polyclonal Abs produced by infected B cells]
what 2 kinds of serology (based on time frame) can be used to diagnose EBV (gamma herpes)?
early: anti-viral capsid antigen
3-6 weeks post infection: anti-EBV nuclear antigen
which herpes virus does this describe?
- rare, NOT ubiquitous
- associated with several lymphoproliferative disorders (Kaposi’s sacroma)
- AIDs-associated virus
Human Herpesvirus 8 (HHV, gamma herpes): aka Kaposi’s sarcoma virus
AIDs associated virus, rarely found in healthy individuals
associated with: Kaposi’s sarcoma, Body Cavity Lymphoma, Multicentric Castleman’s Disease
HHV8 (gamma herpes) is also known as
HHV8 = Kaposi’s sarcoma virus
rarely found in healthy individuals, associated with several lymphoproliferative disorders (Kaposi’s sarcoma, Body Cavity Lymphoma, Multicentric Castleman’s Disease), AIDs-associated
