10. Herpes Virus Flashcards
Herpesviruses
• ____ viruses
• Three flavors - ____, beta, ____ herpesviruses
• ____ DNA, approximately 100 genes
• ____ capsid, lipid ____, ds DNA
• ____ with their hosts, well adjusted pathogens
• Ubiquitous, all ____ species and ____ too! (e.g. oysters)
• ____ infections are a hallmark (herpes is forever)
• Everyone's got herpes - fish, chikckens, elephants, oysters (bivalves)
DNA alpha gamma ds icosahedral envelope co-evolve vertebrate invertebrates latent
Three “genera” of herpesviridae
• Alpha herpes viruses ____, ____, ____ – Grow ____-many are ____
– Latency in ____ neurons
• Beta herpes viruses ____
– Cytomegaloviruses (large ____ cells)
– Grow ____
– Latency in ____ glands, kidneys, lymphocytes
• Gamma herpes viruses ____ KS
– Lymphoproliferative diseases – Latency in ____ cells
* Latency > shed among eveeyr herpes virus * VZV > varicella zoster > \_\_\_\_ and \_\_\_\_ * Beta > originally found in salivary glands
HSV1 HSV2 VZV rapidly cytolytic sensory
HCMV
balloon-like
slowly
salivary
EBV
lymphoid
chicken pox
shingles
Eight human herpesviruses
• HSV1 (primary infection, oral cold sores) (____)
• HSV2 (genital herpes, primary and recurrent sores)
(____)
• VZV (chicken pox, shingles) (____)
• CMV ( retardation, deafness, CMV retinitis, organ transplant rejection) (____)
• HHV6 & 7 (____) - developing important clinical diseases-B cell lymphotropic virus and Roseolovirus
• EBV (mononucleosis, cancer) (____)
• HHV8 (Kaposi’s sarcoma) (____)
• Deep sequencing of fecal material > multiple herpes viruses that they haven't figured out what they are yet (not these eight)
alpha alpha alpha beta beta gamma gamma
Latent, Recurrent Infections Typical of Herpes infection
- initial acute infection followed by ____
• Host immune response clears most virus but virus genome persists. Often in immunologically protected cells (____ system)
• Stress, immune suppression reactivates latent virus
• Reactivation may/may not produce ____
• Virus is shed constantly without ____ disease (____-infection)• Types of general infections in human where if you look over time > initial infection (virus production) > symptoms > large amount of virus made
• Virus is not cleared > virus goes latent in some organ
○ Genome persists
• ____ events over time > can be weeks, months, years for th eintetval
• After primary > lesion (cold sore) > contain vrius; but then times where you produce DNA/virus and no lesions
• Look at extended times over humans (for STD, for example) > vaginal swabs > each participiant will have virus at different times > constant shedding of virus with no symptoms
• With simplex > ____ is unusal > unless immunocompromised
quiescence nervous symptoms clinical persistent
cyclic
death
Herpesvirus Architecture: All herpesviruses have the same basic structure-different genomes
* Yellow > lipid \_\_\_\_ containing glycporteins * Surround that > tegument (orange) > two functions: it's a glue to affix \_\_\_\_ to membrane, and bioloigcal activity in infected cell, when transported to nucleus > subvert the cell from making host proteins to making \_\_\_\_; swithcing clock of virus from host to viral * In capsid > \_\_\_\_
envelope
capsid
viral protein
DNA
Herpes simplex virus infections
• Primary infection mouth, skin, eye - type 1
____ type 2
• Latency: neurons type 1: ____ type 2: ____
RECURRENT INFECTION • Reactivation leads to disease or shedding - \_\_\_\_ - whitlow's finger -\_\_\_\_
Virus survives in immune host • Infects many types of cells • \_\_\_\_ entry glycoproteins • \_\_\_\_ protein receptors on cells • \_\_\_\_ pathways of entry
• Summary of next few slides • Type 1 > virus gows in mouth, skin, eye > can be a major or a minor infection > primary major infection would be kid out of action for 10 days (dehyrdate > have chocolate milksahkes) • Virus replicates in local area > migraates up axon of trigeminal nerve ganglion > innervates 3 regions (opth, max, man) > can get recurrence of infection in these areas ○ Virus sits in neruons, and in a state of latency > controls maintence in neuron • And reactivation > stress, etc > virus starts to \_\_\_\_ in neruons > rides down neuron to the site of reactivation (cold sore) > usually in se area where you've always had it • \_\_\_\_ > dentists without gloves, in the oral cavoty virus is shed > can drive virus into cuticle of giner > get primary infection, and thtne recurrences
genital trigeminal sacral cold sore keratitis
4
2
2
replicate
whitlow’s finger
HERPES SIMPLEX - Type 1
PRIMARY INFECTION
- Usually ____ throat, fever, eye infections and, rarely, Encephalitis (major problem for ____).
- Latest evidence: 60% of new genital infections are due to ____
- Occasionally genital > important for genital herpes > 60% of genital infections is due to HSV1 (oral form)
- HSV1 is the major cause of ____ in US bc of recurrences > immune system tries to rid the virus > ab-antigen complex formation in eye > blindness (via ____, and aggregates)
sore neonates HSV1 blindness scarring
HERPES SIMPLEX - Type 1
LATENT INFECTION
1. Asymptomatic - Virus is detected in between episodes of disease-”____ of virus”
2. ____ Viral DNA resides in sensory cells of ____ nerve ganglion.
• Asymptomatic > no \_\_\_\_
shedding
trigeminal
lesion
HERPES SIMPLEX - Type 1
RECURRENT INFECTION
1. Virus replicates and travels down sensory nerve fiber to infect epithelial cells around the nose and mouth
2. Symptoms are usually a ____ form of primary infection
• Symptoms are milder > each recurrence > you're boosting the \_\_\_\_; doesn't clear the virus but it does act to mitigate the ifnection > which is why recurrent is almost always in midlder form of disease
milder
immune system
HERPES SIMPLEX - OCCASIONAL Type 2
PRIMARY INFECTION
NORMAL
1. Usually ____ eruptions on the genitalia
2. Spread by ____ contact
3. Affects both ____
4. Less frequently (30%) found as ____ (cold sores)
* By 50 > \_\_\_\_% of pop infected with type 1; and not 70% infected with type 2; more select [????] * Reduction in number of people who are HSV1 positive > people have become aware of \_\_\_\_ (from stigma of genital infection)
vesicular sexual sexes herpes labialis 70 HSV
HERPES SIMPLEX - Type 2
LATENT INFECTION
• 1. ____ of virus is common
• 2. Viral DNA resides in sensory cells of ____ ganglia -
• RECUURENCE
• ____ outbreak generally in same location in genital area
• Can lump 1 and 2 as same virus, but a little different, but they're really different; look alike, act similarly, but they're really different viruses
shedding
sacral
milder
HSV “VIRUS SHEDDING”
HSV is shed from normal-appearing oral or genital mucosa or tears.
Transmission occurs from contact with an infected partner who does not have visible ____ and who may not know that they are ____.
In persons with asymptomatic HSV-2 infections, genital HSV shedding occurs on ____% of days, compared to ____% of days among those with symptomatic infections.
In genital infections: HSV Type 1 = 3 to 5% HSV Type 2 = 15 to 20% In oral (mouth) infections: HSV Type 1 = 18% HSV Type 2 = 1
• Shedding > major mechanism of \_\_\_\_ of virus • Any vaccine that doesn't affect shedding is undesirable; want to stop shedding from individuals • Asympto HSV2 > 10% of days (within 3 months) virus will shed • Sympto HSV2 > • Iff asympto all the time > you can still be shedding; once sympto > can have lesions, but can have times when you're just shedding ○ Have a lesion > infecitous; no lesion, you may be infectious • Numbers for 1/2 are probably the same?
lesions
infected
10.2
20.1
Neonatal Herpes Simplex (1)
- Incidence 1/4000 live births in U.S.
- Baby is infected perinatally during passage through the ____.
- The risk of perinatal transmission is greatest when there is a ____ (new) infection in the mother.
- Smaller risk from ____ (old) lesions in the mother, probably because of the lower ____ load and the presence of specific ____.
- The baby may be infected from oral lesions from the ____, nurse or a ____.
- This is for Herpes Type 2
- Need good titer of virus in birth canal in order to infect > happens whne mother has a primary infection > produce virus and baby infected on the way out
- Mild skin disease to a dissemianted ifneciton > child has no ab; mother has little protection to contribute
birth canal primary recurrent viral antibodies mother herpetic whitlow
Neonatal Herpes Simplex (2)
• Infection varies from mild skin disease to a fatal disseminated
infection.
• Dissemination: the organ involved are ____, adrenals and the ____.
• For Encephalitis (brain infection)the prognosis is particularly severe.
• Many survivors have residual ____.
• ____ is given in all suspected cases.
• Prevention is to offer ____ to mothers with genital HSV lesions.
• C section > offered to mothers with genital infection > increase in \_\_\_\_ is due to this virus
liver brain disabilities acyclovir caesarean section
c-sections
Herpes Simplex 1 or 2 Disease
* Normal maintenance > primary > mucosal > latent and reactivation * If have difficulty controlling the disease > usually HSV doesn't cause viremia; but if there is > dissmeianted infection > CNS \_\_\_\_
encephalitis
Alpha herpesvirus Latency
- Occurs in neurons of ____ ganglia (non-dividing cells)
- Capsid goes in, DNA genome remains in ____ as an episome
- Only one transcript: ____ (function still not clear)
- With stress, productive infection initiated
- Capsids travel back down axon, then enveloped
- Free virus released with or without ____ symptoms
- HSV-1 ____ downregulate immediate early protein systhesis
- Virus has to travel distance to get from skin to neuron and then travel back and forth > system has been developed by virus and host > virus trciks host into accepting it as a normal event at the cells urface > virus rides in ____ fashion and comes back down > ____ for the reoccurence
- Do not need to know viral replication form this
sensory nucleus LAT clinical miRNAs retrograde anterograde
