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34 Cards in this Set
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HSV-1, 2:
Which glycoproteins are responsible for binding and entrance into cells? Binds to? Glycoprotein E= ___ receptor Glycoprotein C= ___ receptor |
Glycoproteins B, D responsible for binding and entrance into cells
Glycoprotein E=Fc receptor Glycoprotein C=binds C3d receptor |
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HCMV Lytic infection cycle
The cycle starts with the virion particle _______ and ______ to the cellular membrane The ______ and the _______ proteins are released into _______, and then transported into the _______ where ______ ___ ________ and cascade of gene expression take place. The assembled ____-containing capsid is then transported into ______ and gain _______ and ________ in the trans golgi network. The enveloped capsid is eventually released into extra-cellular media to become infectious virion particle. |
The cycle starts with the virion particle binding and fusing to the cellular membrane
The capsid and the tegument proteins are released into cytoplasm, and then transported into the nucleus where viral DNA replications and cascade of gene expression take place. The assembled DNA-containing capsid is then transported into cytoplasm and gain tegument and envelope in the trans golgi network. The enveloped capsid is eventually released into extra-cellular media to become infectious virion particle. |
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The Herpes virus family
single stranded/double stranded? DNA/RNA? Other features? |
-A large ds DNA genome, capsid and a proteinacious layer over the capsid called tegument.
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Herpes Viruses: Latency
T/F All herpes viruses are able to persist for the life of the host Virus remains ________ in the host as an _______ Limited viral gene expression: restricted to ____ T/F Latent state known for release of infectious virus Latency due to? Latency occurs within what cell types? What leads to reactivation? Signs/Symptoms that precede reactivation? |
True
All herpes viruses are able to persist for the life of the host Virus remains latent in the host as an episome Limited viral gene expression: restricted to Latency-Associated Transcript Sequence (LATs) False No infectious virus produced during latent state Latency due to failure to initiate IE gene expression Latency occurs within small numbers of specific cell types that depends on the virus Expression of latency-associated genes only Reactivation a consequence of cellular signals and leads to production of infectious virus Reactivation may or may not be accompanied by signs or symptoms |
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Herpesvirus Epidemiology / Transmission
Survive in environment? Transmission requires? Susceptible sites? (3) Symptoms during transmission? |
Do not survive well in environment
Transmission requires direct inoculation of virus-containing body fluid into susceptible tissues of uninfected individual Susceptible sites: all mucosa, respiratory tract, bloodstream Ubiquitous viruses: few escape infection Most transmitted asymptomatically - HSV: asymptomatic reactivation on 0.5-1% of days - VZV: transmitted symptomatically |
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Herpes Simplex virus (HSV) 1 & 2:
HSV 1 (_______): Transmitted by? Association of Infection and socioeconomic class? HSV-1 Abs rise in what age group? __-___% adult seroprevalence Recurrent attacks: __-__% |
HSV 1 (Labialis)
- Transmitted by close contact - Frequency of infection inversely correlated with socio-economic level - richer and more affluent you are, the less you get it - HSV-1 Abs rise during childhood - 40-90% adult seroprevalence Recurrent attacks: - 20-40% |
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Herpes Simplex virus (HSV) 1 & 2:
HSV 2 (________) Transmitted by? ___% primary infection subclinical HSV-2 Abs rise starting at _____ (developmental milestone) Neonates infected when? __-__% seroprevalence Previous ____ infections reduces the risk of HSV-2 infection Recurrent attacks __-___% |
HSV 2 (Genitalis)
Sexually transmitted 90% primary infection subclinical HSV-2 Abs rise starting at puberty Neonates infected at birth 20-25% seroprevalence Previous HSV-1 infections reduces the risk of HSV-2 infection Recurrent attacks 60-90% |
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Pathophysiology of Herpes Labialis
3 phases? |
a. Primary Infection (fever, malaise, myalgias, LAD)
b. Latent Phase c. Recurrence |
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Results of Primary Infection with HSV-1
90% are _______? 9% have _____ _______? 1% develop _________ ? What are some of the manifestations? (8) |
90% are asymptomatic
9% have minor illness 1% develop disease: - gingivostomatitis - keratitis - gladiatorum - esophagitis - whitlow - encephalitis - eczema herpeticum - genitalis |
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Herpes Simplex Encephalitis
Age(s) affected? ____ <20, ___>50 Younger patients: associated with ______ infection; older ones associated with ________ infection What proportion seen with primary infection? and with reactivation? Seasonal variation? Which HSV type accounts for 96% of all Herpes simplex encephalitis in adults? |
Most common cause of endemic encephalitis in US
Annual incidence: 1/250-500,000 with 1-2000 cases annually May occur at any age: 1/3 < 20y; 1/2 > 50y Younger patients: associated with primary infection; older ones associated with reactivation infection Primary infection (1/3) vs. reactivation (1/2) No significant seasonal variation HSV-1 accounts for 96% of all Herpes Simplex encephalitis in adults |
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Herpes Simplex Encephalitis
Acute (<1week duration) findings? Behavioral syndromes associated with HSV-1 encephalitis? What psyc symptoms are associated during the initial phase of HSV-1 encephalitis? Behavior alterations may include? KBS is a behavioral syndrome that includes "_______" loss of normal ______ and _______ responses, and increased ______ activity. KBS and amnesia are felt to occur because of viral affinity for the _______ lobe and ______ structures. Over 90 percent of patients will have one of the above symptoms plus _____. HSV-1 CNS infection has also been implicated in cases of recurrent ________ encephalitis. This condition is characterized by upward gaze palsy, facial numbness as well as signs of involvement of corticospinal, spinothalamic, lemniscal, and ______ pathways. |
Focal neurologic findings are usually acute (<1 week in duration) and include altered mentation, altered level of consciousness, focal cranial nerve deficits, hemiparesis, dysphasia, aphasia, ataxia, or focal seizures.
Various behavioral syndromes have been reported in association with HSV-1 encephalitis including: Hypomania, Kluver-Bucy syndrome (KBS), Varying states of amnesia. Hypomanic symptoms often occur in patients during the initial phase of HSV-1 encephalitis, presumably from inflammation of the inferomedial temporal lobe or limbic system. Behavior alterations may include an elevated mood, excessive animation, decreased need for sleep, inflated self-esteem, and hypersexuality. KBS is a behavioral syndrome that includes "psychic blindness," loss of normal anger and fear responses, and increased sexual activity. KBS and amnesia are felt to occur because of viral affinity for the temporal lobe and limbic structures. Over 90 percent of patients will have one of the above symptoms plus fever. HSV-1 CNS infection has also been implicated in cases of recurrent brainstem encephalitis. This condition is characterized by upward gaze palsy, facial numbness as well as signs of involvement of corticospinal, spinothalamic, lemniscal, and brainstem cerebellar pathways. |
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Herpes Simplex Encephalitis
Diagnosis by? (2) Serology useful? Viral culture of CSF? CSF HSV Ag ELISA? |
Diagnosis
- CSF PCR - Brain biopsy - Viral culture - Histology - Serology: unhelpful - Viral culture of CSF: 4% positive - CSF HSV Ag ELISA: 80% sens. 90% spec. Differential Diagnosis (CASG) - Viral encephalitides other that HSV-1 (13%) - Treatable diagnoses other than HSV-1 (<9%) - No diagnosis (33%) |
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Herpes Simplex Encephalitis
What is the preferred standard for diagnosis now? used to be? Are CSF Ab titers useful? Empirical _______ does not affect ability to diagnose HSE during first __-___hrs Histology: acute encephalitis with _______ __________ (also seen with EBV, coxsackievirus, LCM, SSPE, Reye’s syndrome); Serology and CSF viral culture useful? CSF ELISA needs to be done within first ___ days of illlness |
Biopsy used to be gold standard: viral culture of CNS tissue 96-100% sens; 100% spec.
CSF Ab titers NOT useful for HSV as Ab may become detectable only as virus is cleared. Empirical acyclovir (ACV) does not affect ability to diagnose HSE during first 24-48hrs Histology: acute encephalitis with intranuclear inclusions (also seen with EBV, coxsackievirus, LCM, SSPE, Reye’s syndrome); EM 45% sens, 100% spec.; direct IFA 70% sens., 98% spec. Serology and CSF viral culture useless CSF ELISA needs to be done within first 3 days of illlness |
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Herpes Simplex Encephalitis
Treatment: reduces mortality from __ to __% - ________ (anti-viral agent) - 10-12.5 mg/kg i.v. q8 hours x 21d - Modify dose in renal failure? Toxicity: (5) |
Treatment: reduces mortality from 70 to 20%
- Acyclovir - 10-12.5 mg/kg i.v. q8 hours x 21d - No need to modify dose in RF Toxicity: Crystalluria and RF (inadequate hydration) - MS changes, phlebitis, elevated LFTs Acyclovir RX is NOT a diagnostic trial Acyclovir treated pts may still have significant impairment |
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Some Important Points about acute HSV-1
Incubation periods range from _ to __ days Primary infection in children is a _____ (focal/systemic?) illness Disease lasts __-__ days with what symptoms? Common route of acquisition? Herpes keratitis takes _-_ weeks to heal |
Incubation periods range from 2 to 12 days
Primary infection in children is a systemic illness Disease lasts 10-14 days with no sequelae Autoinoculation of alternative sites is common Herpes keratitis takes 2-3 weeks to heal |
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Herpes Labialis
Recurrent? - Systemic symptoms? - Prodrome? - Heals in? - Frequency? |
Recurrent disease
- No systemic symptoms - Prodromal pain, burning, itching (6-53 hrs) - Predictable triggers - Heals in 5 days - Frequency: 1/mo (24%) to 2/yr (19%) |
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Herpes Genitalis
Primary episodes |
Primary episodes: fever, HA, malaise, myalgias, pain, pruritis, dysuria, d/c, LAD
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Some Important Points about HSV-2
Incubation periods range from _ to _ days Extragenital lesions? ________ can lead to urinary retention, neuralgias, obstipation Lesions persist for how long? In primary perianal HSV-2 infection, ______ is the primary symptom |
Incubation periods range from 2 to 7 days
Extragenital lesions in 10-20% Herpetic sacral radiculomyelitis can lead to urinary retention, neuralgias, obstipation Lesions persist for several weeks In primary perianal HSV-2 infection, pain is the primary symptom |
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Genital HSV
Recurrences: - Common? - Do patients shed when asymptomatic? Complications? |
Recurrences
- Occur in up to 90% - Rate: 1.9-2.7 per 100 days - Asymptomatic shedding detected by PCR on approximately 20% of days Complications- - Aseptic meningitis (HSV-2) - Encephalitis - Neonatal infection: 1 in 2-10K - Disseminated infection - Bacterial Superinfection |
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HSV Infections in the IC patient
Infections can involve _______ and _______ tracts and result in (4) presentations Prominent feature of patients with what disease? |
Reactivate frequently and be progressive
Infections can involve respiratory or GI tracts and result in tracheobronchitis, pneumonia, esophagitis or hepatitis Prominent feature of patients with advanced HIV-1 (AIDS) |
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Diagnosis of HSV Infection
______ _____ - cytopathic effect in 48-96 hours ______ - more sensitive than viral culture - Especially useful to diagnosis ____ __________ ________ - Newer tests are type-specific, based on glycoprotein G - Reference tests are? (name some) Which of these is used to identify asymptomatic carriers, neonates? |
Viral isolation: cytopathic effect in 48-96 hours
PCR: more sensitive than viral culture - Especially useful to diagnosis HSV encephalitis Serology - Newer tests are type-specific, based on glycoprotein G - Reference tests are western blot, immunoblot, mAb blocking ELISA, and lectin-purified ELISA - Used to identify asymptomatic carriers, neonates (IgM) Immunofluorescent staining using type-specific Abs |
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Varicella-Zoster virus (VZV)
Causes ___ distinct diseases ___________: primary infection ___________: recurrent infection Five families of glycoproteins (gpI-V) Infectivity neutralized by ______ directed at ______ Virus spreads from cell to cell by? ________ are only known reservoir |
Causes two distinct diseases
Varicella (chickenpox): primary infection Herpes zoster (shingles): recurrent infection Five families of glycoproteins (gpI-V) Infectivity neutralized by mAbs directed at gpI-III Virus spreads from cell to cell by direct contact Humans are only known reservoir |
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Epidemiology of Varicella-Zoster virus (VZV) in the US: Chickenpox
Incidence has ______ sharply since introduction of __________: down 84% by 2000 Seasonal?: Peak in late _____ – early _____ Maximum attack rate age _ – _ years; ______ only known reservoir Contagious? Transmitted how? Adult prevalence? |
Incidence has fallen sharply since introduction of varicella vaccine: down 84% by 2000
Peak in late winter – early spring Maximum attack rate age 5 – 9 years; humans only known reservoir Extremely contagious: transmitted via respiratory route 1.5% of cases in adults |
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Primary VZV: Clinical Features
Incubation period = __-__ days Most contagious during the first _ days after illness onset Rash: ____ (2-6 days post onset) before _____ (6-10 days post onset) |
Incubation period = 10-20 days
Most contagious during the first 2 days after illness onset Crops (2-6 days post onset) before scabs (6-10 days post onset) |
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VZV Rash:
T/F involves only the epidermis |
False
Involves epidermis and dermis |
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Primary VZV: Complications
In kids? In adults? Unique features in immune compromised? |
Kids
- Bacterial superinfection - Reye’s syndrome - Cerebellar Ataxia - Congenital VZV (5d/48h) Adults - Pneumonia - Encephalitis - Meningitis IC - More numerous lesions - Visceral dissemination - Pneumonitis common |
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Pathophysiology of VZV
3 Phases of disease |
1. Chicken pox -
2. Latent phase - 3. Herpes Zoster (shingles) |
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Epidemiology of recurrent Varicella-Zoster virus (VZV) in the US: Shingles
Mostly affects what age group? Seasonal? Preferentially occurs in what patient population? |
Incidence of 10-20%; mostly in older individuals (>55 years-old)
No seasonal preference Preferentially occurs in IC: transplant recipients, HIV-1 infected individuals-->dissemination |
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VZV:
_____ and _____ dermatomes most common |
thoracic and lumbar dermatomes most common
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Recurrent VZV: Rash and Complications
_____________: persistent sensory symptoms (pain, numbness, dysesthesias); 10-15% >60 yrs old |
Post herpetic neuralgia: persistent sensory symptoms (pain, numbness, dysesthesias); 10-15% >60 yrs old
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Recurrent VZV: Complications
________________ - Cranial Nerve V “tip of nose --> cornea” - Keratitis - Iridocyclitis - Glaucoma - Neuroparalytic keratitis _____________ - Geniculate gang. - Ext. ear - Ant. 2/3 tongue - Facial palsy |
Ophthalmic Zoster
- Cranial Nerve V “tip of nose --> cornea” - Keratitis - Iridocyclitis - Glaucoma - Neuroparalytic keratitis Ramsay-Hunt Syndrome - Geniculate gang. - Ext. ear - Ant. 2/3 tongue - Facial palsy |
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Diagnosis of VZV
Usually made by? Differential: (3) Dark Field A stain of ______ FAMA, IFA, ELISA, LA? Serology - Uses: (3) |
Usually made by history, exam
Differential: impetigo, HSV, enterovirus DFA stain of scrapings FAMA, IFA, ELISA, LA Serology - Uses: - immune status, vaccine response, acute infection |
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VZV Vaccination
How is the vaccine prepared? Side effects? Recommended for all children at __-__ months Contraindications? |
Live, attenuated (Varivax, 1995)
Well tolerated Recommended for all children at 12-18 months Contraindications: IC, pregnancy, receipt of blood products in last 5-6 mos, active TB, reaction to gelatin HIV-infected kids: CD4>25%, asymptomatic |
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Summary:
T/F All DNA viruses are able to persist for the life of the host. ______ are common features of infections with herpesviruses. Laboratory diagnosis of herpesvirus infection is accomplished via: (3) ___________ patients are at risk for severe herpesvirus infections. |
True
All DNA viruses are able to persist for the life of the host. Rashes are common features of infections with herpesviruses. Laboratory diagnosis of herpesvirus infection is accomplished via: virus isolation, serology and PCR. Immunocompromised patients are at risk for severe herpesvirus infections. |
