Herpes Flashcards
Pathogenesis of VZV
infection, incubation, replication, spread and reactivation/ secondary infection
what happens after primary infection of VZV?
- Virus remain latent in dorsal root gangly
- later in life, after 60, virus is reactivated and risk increases with age.
- onset of shingle more common AND severe in immunocompromised
- VZV vaccine available for 50+ y/o to prevent shingle
According to the CDC, what precautionary measures should you take to prevent spreadingVZV?
- Keep rash covered
- don’t touch or scratch
- Frequent hand washing
- until rash develops crust, avoid contact with pregnant women you have never had chicken pox or varicella vaccine, premature or low birth weight babies, and/or immunocompromised patients
CMV
infection
Infection is usually through mom to fetus or newborn. also get via sex in adulthood.
usually only a problem for immunosuppressed or very young
neonate contract by transplacental transmission, intrauterine, and/or cervical secretions
baby/child contracts by breast milk, saliva, tears, and/or urine
adult contracts by sexual transmission (semen), blood transaction, or bone graft
causes mental retardation, deafness, neuropathy, pneumonia, retinitis and microcephaly
CMV
cytomegalovirus (HSV-5).
most are infected by middle adulthood
primary infection can result in mono like symptoms
may account for 1/5 of “mono” cases
most common viral congenital infection
4000/yr show symptoms of in utero infection
CMV latency
Established latent infection in many cells, including immune cells- lymphocytes and macrophages.
Virus can be shed in saliva due to chronic replication in salivary glands, for month and even up to 2 years after acute infection
CMV and the immune system
CMV is held in check by our immune system unless there is immunosuppression.
i.e. HIV infection- CMV is the leading cause of death
People on immunosuppressant and receiving organ transplants
EBV
Epstein Barr (HSV-4)
causes most infection cases of mono (79%)
common infection worldwide
frequently seen in high school and college students
“kissing disease”
most people become infected at some point in life
in developing areas in Africa, EBV infection is associated with Burkett’s lymphoma and nasopharyngeal carcinoma
what is infected in EBV?
infection of anti-body producing B cells and makes them hyperproliferate
the infected cells will produce IgM which is detected in the blood (heterophiles lab)
elicit T cell responses that are against the B cells. this causes spleen inflammation and fatigue
Mononucleosis symtoms
Caused by an aggressive T cell response due to the infection and hyper proliferation of the infected B cells
- sore throat
- fever
- swollen lymph glands
- malaise
- sometimes an enlarged spleen or liver
- heart problems (rare)
- CNS problems (rare)
symptoms usually resolve within 1-2 months
remains latent in the throat and blood for the rest of a person’s life
Diagnosis of EBV
patient feels like they have mono
elevated mononuclear WBC count
Heterophiles Ab test: the antibodies that bind non-EBV antigens but are induced by EBV infection.
Staining of cells for viral antigens.
N.B. if a patient has hairy leukoplakia, there is a loss of cytotoxic T cell responses to EBV which leads to a viral re-emergence
Differential Diagnosis between EBV and CMV
CMV is a heterophile negative cause of infectious mono that is most likely confused with EBV infectious mono but usually not accompanied by posterior cervical adenopathy
the CMV infection mono is characterized by its prolonged course of prominent liver involvement.
HHV-6
spread by saliva
present in nearly everyone by adulthood
associated with various neurological problems like MS
possible molecular mimicry of myelin basic protein may stimulate T cell responses that destroy neuron function
Roseola/Exanthema subitum (aka 6th disease) is a rash condition usually occurring in children. Roseola also seen in HHV-7
seems to be linked to Alzheimer’s and infertility
HHV-8
aka Kaposi’s sarcoma associated herpesvirus (KSHV)
causes Kaposi’s sarkoms in people with AIDS
most likely requires immunosuppression
inactivates Rb
HIV Tat protein contributes to development of KS
Formerly a rare cancer found almost exclusively in Mediterranean and sub-Saharan men
HSV-1 HSV-2 VZV EBV (H)CMV HHV-6 HHV-7 HHV-8
herpes simplex virus 1 herpes simplex virus 2 varicella zoster virus Epstein-Barr Virus human cytomegalovirus Human herpes virus 6 human herpes virus 7 human herpes virus 8 aka Kaposi's Sarcoma virus
how does the herpetic lesion spread?
“creep or crawl”
got it’s names from the way it spreads
how long has herpes virus been around
centuries
one of the most common viruses found in humans
Herpes infection
once an individual has become infected it will remain in the body FOR LIFE
it isn’t always active- it can establish a latent state in an immunocompetent host
herpes structure
enveloped icosohedral capsid/ nucleocapsid dsDNA linear (125-230 kb) pleomorphic tegument
Tegument
in herpes, the tegument is between the envelope and capsid. it contains viral protein that assist viral replication
herpesvirus replication
infect non-replicating cells like neurons
it will replicate in the cell’s nucleus
transcription of viral genome by cellular DNA-dependent RNA polymerase
regulated by viral-encoded and cellular nuclear factors
this interplay will determine is the virus is active or latent
encode their own DNA polymerase and thymidine kinase
what happens when infection is symptomatic?
HSV and VZV replicate in a lytic manner. that is, the cells die and then skin lesions form
what happens when the infection is latent?
it is in specific cells types
only a small number of viral genes are expressed
it can then be reactivated
in latency, the immune system cannot see the virus if noRNA or proteins are being made
what happens when the virus is reactivated
reactivation and visions made
lytic replication results with attendant symptoms
what is thymidine kinase
it is encoded by herpes (along with their own DNA polymerase)
TK will increase nucleotide levels in cells
TK assists in the replication of viral genome in non-replicating cells such as neurons
the target of antiviral drugs
how is it spread?
via cell to cell contact
evades antibodies
what is the immune response that herpes illicit
T cell responses are primarily responsible for resolving initial infection
Antibodies can protect form acquiring infection (VZV vaccine)
The course of disease is often very different in the immune compromised
HSV-1 vs HSV-2
have similar structures and replication
have about 80 genes
primary infection by mucosa to mucosa contact
childbirth (HSV-2)
subclinical infection is frequent
recurrent disease
preference for the mouth, pharynx and genitals
both cause latent infections
HSV-1 reactivation occurs most frequently above the waits and HSV-2 below the waist.
Lesions of HSV-1 and 2 look similar
where does HSV-1 and 2 replicate
1 at the trigeminal ganglia
2 at the sacral ganglia
HSV disease mechanism
initiation of infection by direct contact between mucosal surfaces. cell to cell spread allows for antibody neutralization
replication causes cytopathic effects on the epithelial cells this forms a syncytia
the cell-mediated immunopathological effects contribute to symptoms
HSV established latency in neurons
syncytia
fusion between infected and uninfected cells
HSV reactivation and triggers
from a latent state by various factors
cell mediated immunity is required for resolution of symptoms with a limited role for antibody
-stress, fatigue
-temperature changes
-UV light/sun
=menstruation
-immunosuppression
-Herpes Labialis
- cold sores, most common recurrent HSV infection
Patches of localized vesicles, muccocutaneous junction around the mouth. Painful, annoying, resolve, reappear at the same time
dentists are at risk: lesions in patents not always evident
Virus in saliva of 5% and 2% in adults
-Encephalitis
- if virus gets to CNA (very rare and deadly)
-Keratoconjunctiva
-ocular herpes: affinity for corneal tissue, painful ulcer, recurrences may lead to blindness, immunocompromised susceptible (esp HIV+)
-Herpes gladiastorum
-found in wrestlers and other engaged in contact sports
-Eczema herpeticum
-generalized cutaneous infection of a person with eczema- numerous skin vesicles
Prevention and treatment of HSV infection
prevention- no vaccine: no specific form of prevention. avoid contact with lesions: oral and genital
treatment: acyclovir
ACV is also used for shingles
Acyclovir
nucleoside (guanosine)analog
converted to acyclo-GMP by viral thymidine kinase
Then converted to acyclovir GTP by cellular kinase. Then incorporated into viral genome and DNA synthesizes stopped because new nucleotides cannot be added (chain termination)
lab diagnostic tests
Tzank smear: scrape skin off lesion
looking for syncytial cells= giant cells that are multinuclearted, swollen cytoplasm intranuclear bodies
Viral antigen assays test antibody reactivity
PCR for viral nucleic acid provides definitive diagnosis
HSV-2
Virus can be shed even during asymptomatic periods
practice safe sex
cycler can reduce transmission
pregnant women with active HSV-2 disease is life threatening in children
the cellular immune system is underdeveloped in children
50% mortality
45% of the rest have cognitive impairment
