Herpes Flashcards
What is the structure of herpes viruses?
ds DNA virus (low mutation rate)
Enveloped (doesn’t survive well in environment)
How is CMV transmitted?
person to person/via infected fomites
Intrauterine
Perinatal: present in cervicovag secretions
Postnatal: breast feeding, daycare, saliva, urine
Blood transfusion
Organ transplantation
How does CMV pathogenesis occur?
Infects endothelial cells of GU, upper GI, respiratory tract
Then infects leukocytes & spreads to multiple tissues
Can then become symptomatic disease, asymptomatic infection, or latent infection
Where is the latent CMV reservoir?
Myelomonocytic stem cells
Monocytes
What determines whether patienst have asymptomatic infection or symptomatic disease by CMV?
Usually asmytomatic, except in immunocmopromised patients with impaired T cell immunity
What are the three common manifestations of symptomatic CMV infection?
Infectious mononucleosis
Congenital CMV infection
CMV infection in immunocompromised host (solid organ transplantation, bone marrow transplantation, HIV/AIDS)
What are the symptoms of infectious mono caused by CMV?
Fever, hepatomegaly, lymphadenopathy, malaise, fatigue, splenomegaly, pharyngitis, rash
Lab findings: atypical lymphocytes, lymphocytosis, mild thrombocytopenia, CMV antibodies, heterophile antibodies
CMV is responsible for about 8% of IM cases; EBV is the other common cause
What are the symptoms of congenital CMV infection?
Hepatosplenomegaly, lymphadenopathy, resp distress, blueberry muffin rash, microcephaly, brain damage –> retardation, seizurse, deafness, blindness
Elevated LFT (liver function tests), thrombocytopenia, pneumonitis, CMV in body fluids
What are common manifestations of CMV diseases in immunocompromised host?
Fever, hepatitis, retinitis, pneumonitis, immunosuppression, myelosuppression, encephalopathy, colitis, rejection, graft v host disease
What common disease might be associated with CMV infection?
Atherosclerosis
How is CMV diagnosed?
Serology– IgG and IgM (note that IgM usually indicates a new infection, but in CMV even reactivations lead to an increase in IgM)
Virus isolation, pp65 antigen detection in blood, CMV DNA PCR
What is the treatment for CMV?
Who should get treatment?
Ganciclovir
Valganciclovir
Foscarnet
Cidofovir
All are viral DNA polymerase inhibtors
Used to treat immunocompromsed host
How is HSV transmitted?
Person to person
Intrauterine = rare
Perinatal
Postnatal: skin/mucous membrane contact/viral shedding in saliva, oro-facial lesions
Which strain is more common in oral cavity? GU tract?
HSV-1 in oral cavity
HSV-2 in GU tract
What are the 3 types of infections that HSV can cause?
Primary infection: virus replicates in skin & mucous membranes –> enters nerve endings –> retrograde transport to sensory ganglia –> replication here –> anterograde transport back to mucosal and cutanous sites –> can be released from lesions/ continue to replicate here
Latent infection: reversible interruption of the virus replication cycle in sensory neurons
Reactivation of latent infection: probably due to changes in host; leads to recurrent infections
Why are herpes lesions painful?
Bc they replicate in sensory neurons– causes pain!
What are common clinical illnesses caused by HSV infection?
Less common?
HSV 1:
- *gingivostomatitis** (fever, oral pain, difficulty swallowing, vesicular lesions throughout oral cavity)
- *pharyngitis** (fever, looks like strep, EBV)
- *labialis** (cold sores)
HSV 1 or 2:
- *herpes genitalis** (painful genital ulcers)
- *neonatal herpes** (vesiculoulcerative lesions on skin, eyes mouth, encephalitis, or disseminated infection)
Less common: encephalitis, keratitis, retinitis, gladiatorim (wrestler’s herpes), herpes whitlow (finger), eczema, disseminated herpes, erythema multiforme, bells palsy,
Possibly schizophrenia, alzheimer’s
How is HSV infection diagnosed?
IgG, IgM
Virus isolation
Antigen detection
DNA PCR
Clinical diagnoses= unreliable
How do you treat HSV?
Oral acyclovir, valacycolvir (its prodrug), or famciclovir (penciclovir prodrug)
Topical acyclovir/penciclovir
IV Acyclovir
** these drugs are very safe. all are viral DNA pol inhibitors
How can you prevent herpes infection- neonatal? Genital?
Neonatal: C-section
Genital: condoms, valacyclovir by infected partner
What are the 3 categories of herpes infections? Features? Examples?
Alpha: short replication cycle, variable host range, latent in sensory neurones
HSV1, 2, VZV
Beta: long reproductive cycle, narrow host range, latent in lymphoid cells & others
CMV, HSV6, HSV7
Gamma: narrow host range, latent in lymphoid cells, associated with tumors
EBV, HSV8= KSH
What diseases does VSV cause?
Varicella= chicken pox
Zoster = shingles
What type of rash is VSV?
Vesicular
Highly infectious
How does VSV spread in cells?
Cell to cell OR from free enveloped particle
This is important bc it can remain intracellular and still spread – antibodies can’t reach it, making cellular immunity critical for host defense against these viruses
What is the structure of herpes viruses?
Enveloped
Icosahedral capsid
DNA genome- ds
Where does VSV get its final envelope in the cell?
The transgolgi network
What is varicella?
Chicken pox- vesicular rash, sheds contagious virus particles which can infect another person via airbourne route
What is zoster?
Shingles - reactivation of VSV after its been latent post- varicella infection
Presents as vesicular rash, dermatomal distribution, doesn’t cross the midline. Rash is infectious
Happens in the elderly or immunocompromised
When can VSV be dangerous i.e. which people?
Congenital infection– when mom gets it during pregnancy; affects many organ systems, baby often dies
In immunocompromised: more severe illness, can be fatal
What happens to make VSV latent?
Stays in the dorsal root ganglia
Expresses only a few genes
Not “lytic”
How can you diagnose VSV?
immunofluorescence on a smear of the vesicular fluid
PCR of vesicular fluid
Culture
How can you prevent VSV?
Vaccine: live attenuated vaccine
It’s the only herpes virus for which there is a vaccine
How can you treat VSV? Who should get treatment?
Acyclovir– requires higher does than for HSV; not that it works best for HSV-1>HSV-2>VSV
SE include Gi symptoms, neuro symptoms, bone marrow suppression
What cancer is associated with EBV?
Burkitt’s lymphoma
Think: EBV infects B cells and causes Burkitt’s
What disease is caused by EBV?
Symptoms?
Treatment?
Infects B cells and causes infectious mononucleosis, nasopharyngeal carcinoma, lymphoma (including Burkitt’s), oral hairy leukoplakia, post-transplant lympho-proliferative disease
Latency develops in memory B cells after mono
What are the symptoms of infectious mono?
Fever, lymphadenopathy, hepatosplenomegaly, exudative pharyngitis, fatigue, rash after treatment with ampicillin
How do you diagnose infectious mono?
Serology
What is roseola?
Acute illness in infants - rash, fever, seizures; latent in CNS
What is herpes virus 8?
Closely related to EBV - gamma virus
Causes Kaposi’s sarcoma in the elderly/HIV infected
Which herpes infections cause congenital illness?
Neonatal?
Congenital = CMV, VSV
Neonatal = HSV, VSV
** VSV can do both
