Virology 8 Herpes Virus Flashcards

1
Q
  1. List the herpes viruses that infect humans.
A
Herpes simplex 1 and 2
Varicella zoster
Epstein-Barr virus
Human Cytomegalovirus
Human Herpes virus 6,7,8
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2
Q
  1. Identify the tissues tropisms that separate these viruses into broad groups.
A

two groups are separated based on their tropism and site where latent virus is maintained
neurotropic (HSV 1 and 2 and Varicella zoster)
lymphotrophic (other herpes)

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3
Q
  1. Discuss how herpes viruses are transmitted, how this affects our ability to deal with these infections, and the implications for society.
A

virus is shed in bodily secretions or sloughing of infected cells (sex, kissing, breast milk, GI and, for varicella, airborne)

are ability to deal with infection is often limited by whether symptoms are present

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4
Q
  1. List and describe the diseases caused by Herpes Simplex Virus 1.
A

infects any mucosal surface or skin area

most common manifestation is gingivostomatitis (ulcers on the mouth or lips)
development of ulcers: pain or tingling–erythematous spot–vesicle fluid— ulceration

keratitis (keratoconjunctitivitis) leading cause of infectious blindness in US (infection causes clouding of the cornea)

leading cause of sporadic viral encephalitis in US: malaise, confusion and coma, necrotic lesions of the temporal lobe (70% without antivirals, 30% with, the earlier the better)

herpetic whitlow: dentists’ infection on finger tips
herpes gladiatorum: infection on the cheek
disseminated infections in severely immunocompromised patients

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5
Q
  1. Explain the concept of latency an how it differs in lymphotrophic herpes virus
A

lymphotrophic herpes viruses accomplishes latency by maintaining their genomes as episomal elements that reside in the nucleus of latently infected cells (it does not integrate); 5-6 genes are required to accomplish replication and segregation in lymphoid cells

these viruses use immune suppression mechanisms including preventing of MHC antigens on surface, encode IL-4 or IL-10 (immunosuppressive), decoy cytokine receptors and prevent degradation of viral proteins (and also presentation)

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6
Q
  1. Discuss the implications of latency in transmission of infection and the impact of high rates of asymptomatic shedding and primary infection.
A

high rates of asymptomatic infection and shedding of the virus are important for its spread, which makes partner/partner spread difficult to prevent based on symptoms and makes vaccine development difficult (designed to prevent symptoms not infection)

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7
Q
  1. Explain HSV latency with regard to reactivation triggers and the consequences of reactivation.
A

in neurotropic viruses, if the neuron (host cell state is critical) becomes “permissive” once the virus has undergone retrograde transport, anterograde transport is then possible (viral particles are released and can re-infect epithelium)

triggers include fever, stress, nerve trauma, changes in steroid hormone levels and UV light (all potentially stress out the neuron)

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8
Q
  1. Identify those herpes viruses that cause cancer in humans and briefly explain their role in neoplastic disease.
A

EBV is a co-factor in Burkitt’s lymphoma (solid B cell tumor) usually effects very young children up to 10 yo, if B cells are infected with EBV at time when rag genes are active, the virus prolongs expression (important in the rearrangement of immunoglobulin gene segment, c-myc activation)

EBV is also a co-factor in the development of nasopharyngeal carcinoma (epithelial cell)

American's Burkitt's (rare)
EBV lymphomas (post transplant lymphoproliferative disease) seen in AIDS patients as well as oral hairy leukoplakia 

EBV may be associated with Hodgkin’s disease and gastrointestinal cancer

HHV-8 is associated with kaposi’s sarcoma, a tumor involving vascular endothelial cells,

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9
Q
  1. List and describe how herpes virus infections are diagnosed.
A

simplex infections dx. by characteristic appearance of the lesions

Tzanck test was used in identifying cytopathology in cells scraped from ulcers; alternatively you can use antibodies to glycoprotein G to distinguish HSV1 and HSV2

herpes encephalitis most recently uses PCR test of CSF

chicken pox dx. on basis of characterisitic rash

EBV mono can be dx with a rapid latex agglutination test, heterophile antibody tests are more sensitive, diagnostic “downy cells” can be ID’d

HCMV infection usually determined by PCR, IMF or IHC, diagnostic “owl eye cells”

no lab tests for HHV 7 and 8

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10
Q
  1. Define heterophiles antibody and discuss the significance of the terms “heterophile positive” and “heterophile negative” negative mononucleosis.
A

heterophile positive refers to the host B-cells making antibodies, some of which are reactive to sheep blood and that was used as a diagnostic tool

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11
Q
  1. List the vaccines available to prevent herpes virus disease.
A

vaccines for only varicella zoster virus, to prevent chickenpox infection and shingles reactivation are available currently

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12
Q

List the members of the alpha, beta and gamma herpes groups.

A

alpha: neurotropic viruses
beta: HCMV, HHV 6, 7
gamma: EBV and HHV-8

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13
Q
  1. Explain the concept of latency an how it differs in neurotrophic herpes virus
A

neurotropic viruses (terminally differentiated) so virus can shut off the expression of all viral proteins (difficult for host to target and eliminate)- true latency expresses only one gene (latency associated transcript) which prevents apoptosis of the latently infected neuron

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14
Q
  1. List and describe the diseases caused by Herpes Simplex Virus 2.
A

most common manifestation of ulcers on the genitalia (clustered on the shaft for men, for women, external genitalia or walls of the vagina or cervix or perineum)
dysuria in women, (HSV-1 infection of genitals is generally less severe)

can develop signs of aseptic menigitis (self limiting)
neonatal herpes is highly lethal (70% if untreated), survivors can have neurological sequalae (infection spreads to all tissues due to immature immune system (in utero infection rare)

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15
Q
  1. List and describe the diseases caused by Varicella Zoster virus.
A

chicken pox (enters through respiratory route or direct contact of mucosal surface), disseminated infection seeds the skin (development of ulcers) and internal organs

ulcers are similar to HSV1 except they tend to scab over and itchy intensely (can induce scarring or staph/strep infection) tx. with baking soda baths or calamine lotion

vaccine altered disease: rash can appear but is highly attenuated and restricted to a few lesions on the skin

reactivation causes zoster or shingles (painful rash over an entire dermatome) development from painful sensation to erythema, vesicles then ulcers (vesicle fluid is very infectious) can take up to a month to clear

post herpetic neuralgia: intense pain in the dermatome where the outbreak occurred (months), and antivirals can be used to reduce the pain

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16
Q
  1. List and describe the diseases caused by Human Cytomegalovirus.
A

cytomegalic inclusion disease (congenital infection)
HCMV is the leading cause of birth defects in the US: hemolytic anemia, thrombocytopenia, hepatitis, splenomegaly, rashes and mental retardation

most common heterophiles negative mononucleosis: fever, malaise, sore throat, lymphadenopathy (and hepatitis)– self-limiting and often asymptomatic

immunocompromised: solid organ transplants can lead to infection, HIV patients can develop blinding retinitis, interstitial pneumonitis due to HCMV is the second leading killer of bone marrow transplants

17
Q
  1. List and describe the diseases caused by Ebstein-Barr Virus.
A

heterophiles positive mononucleosis: fever, severe malaise, sore throat, consular exudates and petechia on the palate, splenomegaly and lymphadenopathy (some asymptomatic infection)

EBV is a co-factor in Burkitt’s lymphoma (solid B cell tumor) usually effects very young children up to 10 yo, if B cells are infected with EBV at time when rag genes are active, the virus prolongs expression (important in the rearrangement of immunoglobulin gene segment, c-myc activation)

EBV is also a co-factor in the development of nasopharyngeal carcinoma (epithelial cell)

18
Q
  1. List and describe the diseases caused by Human Herpes Virus 6 and 7.
A

typically acquired at a young age; cause of roseola infants (macular rash, fever, self-limiting)

some asymptomatic infection, can be very serious in organ transplant patients/ disseminated infection

19
Q
  1. List and describe the diseases caused by Human Herpes Virus 8.
A

Kaposi’s sarcoma- associated herpes

tumor involving vascular endothelial cells, dark purple to brownish lesions develop at numerous sites in the body as a direct result of infection of cells (virus encodes several for proliferation and transformation); predominantly in AIDS or older persons (endemic to Mediterranean)

spread by sexual activity but appears very hard to transmit, infection also requires diminished immunity

20
Q

Discuss antivirals that are available for treatment of herpes virus infection.

A

all target the viral polymerase and are nucleoside analogs (except foscarnet) causing chain termination during DNA synthesis, or inhibiting viral polymerase

found to be safe used for long term prophylaxis to suppress reactivation (except focarnet)

used primarily in HSV1 and 2, can be used in higher concentrations against VZV and EBV, especially in infection of immunocompromised

ganciclovir and foscarnet are effective against HCMV, higher toxicity (retinitis and interstitial pneumonitis)

INF can be used for HHV-8, but best therapy is to restore the host immune system