Herpes Virus Flashcards
What are the alpha herpesviruses?
HSV-1 (HHV-1)
HSV-2 (HHV-2)
VZV (HHV-3)
What are the beta herpesviruses?
CMV (HHV-5)
HHV-6
HHV-7
What are the gamma herpesviruses?
EBV (HHV-4)
HHV-8
What is a characteristic of alpha herpesviruses?
Blistering rash, neurotropic
What is a characteristic of beta herpesviruses?
Roseola viruses (CMV is transient)
What are the lymphotropic herpesviruses?
EBV, CMV, HHV-6, HHV-7, HHV-8
What is the difference between lymphotropic and neurotropic herpesviruses?
Lymphotropic - can infect epithelial cells
Neurotropic - can infect nerve cells
What is contained within the CMV tegument?
pp65 and mRNAs
What makes CMV genetic makeup unique compared to other herpesviruses?
Contains DNA and RNA
What is the function of immediate early genes of CMV?
Function in viral DNA synthesis
Do not require protein synthesis
Detected in nucleus within a few hours
What is the function of early genes of CMV?
Function in DNA replication and viral protein modification
Require protein synthesis for expression
Cytoplasmic and nuclear
What is the function of late genes of CMV?
Mostly structural gene products (capsid, tegument, envelope)
Cytoplasmic and nuclear
What cells get permissive infection of CMV?
Fibroblasts, epithelial cells, macrophages
What cells get latent infection of CMV?
Hemopoietic cells (including myeloid/macrophage progenitor cells in the bone marrow and liver)
What cells get persistent infection in CMV?
Lymphocytes, endothelial cells, stromal cells of he bone marrow
What is the leading infectious cause of birth defects in the US?
CMV
Who will exhibit clinical symptoms of CMV infection?
Immunocompromised patients
Older individuals (immunosenescence)
Neonates
What is the mode of transmission of CMV?
Bodily fluids
What are the clinical manifestations of CMV in immunocompetent host?
Asymptomatic (80-90%)
Mononucleosis (heterophile antibody negative)
Idiopathic thrombocytopenic purpura/hemolytic anemia
What are the clinical manifestations of CMV in immunocompromised host?
Retinitis - hemorrhagic
Hepatits
Gastroenteritis - primarily colitis and esophagitis
Pneumonia - diffuse interstitial/alveolar, “snow storm”
Glomerulopathy
Disseminated disease
What are rare manifestations of CMV infection?
Periventriculitis
Transverse myelitis/peripheral neuropathy
Cytomegalic inclusion disease of the newborn
How is CMV diagnosed?
Rapid culture (Shell vial method) Histopathology/immunocytochemistry PCR
What do you need for a positive diagnosis of CMV?
Evidence of viral replication (positive shell vial culture or positive PCR)
AND
Systemic signs of disease (fever, leukopenia, thrombocytopenia, eleveated liver transaminases)
What can be used to prevent CMV infection?
Vaccine being developed
What can be used to prevent CMV disease (prevent reactivation of already infected patients)?
Antiviral prophylaxis - ganciclovir, valganciclovir
Bolstering cell mediated immunity
What is most important in the immune response to CMV?
CD8 cytotoxic T cells
What is the primary treatment of CMV?
Ganciclovir
or valganciclovir, foscarnet
What cells are infected by EBV?
B lymphocytes and oral/nasopharyngeal epithelium
How does the DNA persist in cells latently-infected with EBV?
Episome
How does EBV result in malignant transformation?
Viral genome inserted into cell DNA
What are clinical manifestations of EBV infection in immunocompetent host?
Only 10% of infected persons become symptomatic
Heterophile antibody positive mononucleosis
Autoimmune disease - rash with ampicillin
Pneumonitis
Transverse myelitis/peripheral neuropathy
Some Hodgkin’s lymphoma
What is most important in the immune response to EBV?
CD8 cytotoxic T cells
What is the first antibody response (prior to symptoms) of EBV?
IgM/IgG antibodies to early antigens
What is the second antibody response (during symptoms) of EBV?
IgM antibodies to heterophile antigens
What is the subsequent antibody response (resolution) of EBV?
IgM/IgG antibodies to EBNA
What are clinical manifestations of EBV infection in immunocompromised host?
PTLD (post transplant lymphoproliferative disorder)
Hairy oral leukoplakia
Burkitt’s lymphoma
How is EBV diagnosed?
Evidence of high EBV DNA by quantitative PCR
Positive immunocytochemistry
PLUS
Systemic signs of disease - fever, pharyngitis, lymphadenopathy
How is EBV disease prevented (reactivation prevented in previously infected patients)?
Acyclovir
Ganciclovir
Valganciclovir
What is the treatment for EBV mononucleosis?
Supportive treatment
Corticosteroids for severe case
What is the treatment for EBV pneumonitis or EBV hairy leukoplakia?
Acyclovir
What is the treatment for Burkitt’s lymphoma/nasopharyngeal carcinoma from EBV?
Chemotherapy/excision
What is the treatment for PTLD (post transplant lymphoproliferative disorder)?
Acyclovir, ganciclovir, non-specific immunoglobulin, alpha interferon
Anti-CD20 Rituximab
Is VZV lymphotropic or neurotropic?
Neurotropic - reactivation associated with pain or paresthesias
What cells does VZV infect?
Epithelial cells - vesicular (blistering) rash
What are the stages of VZV infection?
Primary infection - chicken pox Latency (90% dorsal root or cranial nerve ganglia, 10% anterior horn cells) Reactivated infection (shingles)
Who is most susceptible to VZV complications?
Most frequent in immunocompromised patients
Also frequent in immunocompetent adults
What are complications of chicken pox?
Most commonly involve CNS, lungs, or liver
Reye’s syndrome - associated with aspirin
Hemorrhagic chicken pox in immunocompromised host
What is shingles?
Vesiculopustular rash involving 1-2 contiguous dermatomes
Prodromal paresthesias or pain
What are complications of shingles in immunocompetent host?
Post-herpetic neuralgia
Decreased vision/blindness (5th cranial nerve)
Encephalitis associated with 5th cranial nerve
Ramsey-Hunt syndrome (geniculate ganglion)
What are complications of shingles in immunocompromised host?
Disseminated disease
How is VZV diagnosed?
Physical diagnosis/history
If doubt after physical: Pap smear of skin lesion, direct fluorescent antibody (DFA) of skin lesion, PCR of CSF
How is VZV infection/disease prevented?
Oka vaccine (live/attenuated)
- Prevent chicken pox in nonimmune children and adults
- Prevent shingles in elderly
VZIG
- Prevention of chicken pox in nonimmune immunocompromised patients (newborns of mothers with chicken pox)
What is the treatment for chicken pox/shingles in immunocompetent host?
Acyclovir
within 24 hrs for chicken pox, within 72 hrs for shingles
What is the treatment for chicken pox/shingles in immunocompromised host?
Acyclovir IV
What cells does HHV-6 infect?
Lymphocytes, epithelial cells, and monocytes/macrophages
What is the clinical presentation of HHV-6?
Exanthem subitum (roseola) - in children
In adults and children:
- Mononucleosis (heterophile antibody negative)
- Meningitis, encephalitis, pneumonitis, hepatitis
- Bone marrow suppression - delayed bone marrow engraftment in BMT patients
How is a diagnosis of HHV-6 disease made?
Characteristic rash (Exanthem subitum - roseola) immediately after 1-2 days of high fever
Serology
PCR
What is the treatment of HHV-6 disease?
Ganciclovir, foscarnet, and cidofovir
What cells does HHV-8 infect?
Urogenital and gastrointestinal epithelial cells
What differentiates HHV-8 from other lymphotrophic herpes viruses?
Also angiotrophic
What form is the DNA in latent HHV-8 infection?
Episome
What are clinical manifestations of HHV-8?
Kaposi’s sarcoma
Primary effusion lymphoma (PEL)
Multicentric Castleman’s disease (MCD)/B cell lymphoma
What immunologic response is important in HHV-8?
T cell mediated immune response
How is HHV-8 diagnosed?
Serology
PCR
What is treatment of cutaneous Kaposi’s sarcoma from HHV-8?
Ganciclovir, valganciclovir, foscarnet
What is treatment of visceral Kaposi’s sarcoma or lymphoma from HHV-8?
Chemotherapy and irradiation
What is treatment of other manifestations of HHV-8?
Improve cell mediated immunity
