Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Virology > Unit 4 -Herpesvirus > Flashcards

Unit 4 -Herpesvirus Flashcards

1
Q

What is the history of Herpesvirus?

A
  • Greek Scholars coined the term herpes, which means to “creep or crawl” in reference to the spreadin gof herpetic lesions
  • Herpesviurs infections have existed for centuries. They are among the most common viruses found in humans.
  • Oncce an individual has become infected by a herpesvirus, the infection remains in his/her body for life.
  • Herpesvirus establish a latent state at a specific site in an immunocompetent host.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What other things are involved in the history of herpes?

A
  • An individual can be infected with more than one herpesvirus during their lifetime.
  • Herpesviruese remain silent for many years only to be reactivated later
  • Infection against one member of the Herpesviridae family does not confer protection against infection or disease with the other members.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the Clinical Signs and Symptoms of Human Herpesviruses?

A

Herpesvirus simplex virus Type 1 (HSV-1) and herpesvirus simplex virus type 2 (HSV-2)

  • Perference for the mouth, pharynx, and genitals
  • Both cause latent infections
  • HSV-1 reactivation occurs most frequently above the waist.
  • HSV-2 reactivation occurs most frequently below the waist
  • Lesions of HSV-1 and HSV-2 look similar
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Herpesvirus simplex virus TYPE 1 (HSV-1)

What are the causes of herpetic diseases?

A

Causes a number of herpetic diseases:

  • Cold sores of the mouth
  • Lesions on the lip
  • Herpes keratitis of the eye (the leading cause of corneal blindness in the United States
  • Herpes gladitorium (transmitted during frequent contact in wrestling)
  • Herpes rugbeiorum (seen in other contact sports like rugby)
  • Causes genital herpes in about 10% of cases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

HSV-1 reactivation is associated with what factors?

A
  • Immune suppresssion by bytotoxic drugs
  • Sexual transmission
  • Physical and emotional stress
  • Temperature changes (e.g. hot or cold)
  • Too much ultraviolet light (sunburn)
  • Menstruation
  • Lactation
  • Malnutrition
  • Excessive fatigue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is involved in Herpesvirus simplex virus TYPE 2 (HSV-2)?

A
  • Causes 90% of all gential herpes cases in the U.S.
  • 45 million perople infected in the US (1 in 5 adolescents and adults)
  • New infections occur at about a rate of 1 million new cases/year.
  • Majority of infections are unrecognized, undiagnosed and untreated.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are HSV-2 Infections?

A
  • Individuals with HSV-2 can shed virus even during asymptomatic periods.
  • Safe-sex practices (condoms) in combo with valacyclovir therapy reduce the spread of HSV-2 during sexual intercourse by 75%.
  • Pregnant women with active HSV-2 should deliver the infant by c-section.
    • Skin rash, fevers mouth sores
    • Eye infections
    • Encephalitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is Varicella Zoster Virus?

(VZV)

A
  • Causes chickenpox and chinges
  • Chickenpox is a mild disease of children but can be severe in infants, adults and persons wiht impaired immune systems.
  • VZV is teh only herpesvirus that spreads person-to-person by coughing or sneezing.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is involved in children pox?

A
  • Symptoms develop 10–21 days after contact with an infected person.
  • VZV infects the skin or mucosa of the respiratory tract and progresses through the blood and lymphatic system to cells found in reticular connective tissue.
  • First sign of disease is the itchy exanthematous (“skin eruption”) rash.

Other Symptoms:

  • Fever
  • Malaise
  • Average of 300-400 lesions on the body during an attack
  • Blisters dry and form scabs in 4-5 days

Adult compications

  • Pneumonia
  • Bacterial infection of the skin
  • Swelling of the brain

CDC recommends taht children be vaccinated at 12-18 months or before their 13th birthday

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is Shingles or Hepes Zoster?

A
  • After a primary VZV infection (chickenpox) the virus remains latent (dormant) in the dorsal root ganglia (neurons of the nerve roots)
  • The virus is reactivated late in life after the age of 60and the risk of reactivation increases with age
    • 1.2 to 3.4 per 1000 healthy individuals
    • 3.9 to 11.8 per 1000 individuals older than 65 years
  • The onset of shingles is more common and severe in immunocompromised patients.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are they symptoms of shingles?

A
  • Severe pain
  • Numbness
  • Itching
  • Followed by a vesicular rash forms in a 3–5 day period
    • The rash follows a nerve on one side of the body.
    • In an otherwise healthy individual, the disease lasts 10–15 days (>30 days for skin to return to normal).
    • The disease can last 3–4 weeks in an immunocompromised patient.
    • Chronic shingles may also occur in AIDS patients.
  • Individuals who have not had chickenpox can contract chickenpox from an individual suffing from shingles
  • One cannot get shingles from someone afflicted with shingles
  • Shingles is caused only by VZV that has been dormant since an individual acquired chickenpox.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is involved in Shingles and nueropathy?

A

Postherpetic neuralgia- pain that lasts for months or years after a shingles infection

  • Mild to very severe; may come and go
  • Described as deep aching, burning, stabbing
  • Increased sensitivity to touch or temperature changes
  • Risk increases with age

Treatments:

  • Anticonvulsant drugs may help
  • Skin patches with lidocaine
  • Pain meds ranging from ibuprofen to oxycodone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is Cytomegalovirus (CMV)?

A

Common in all human populations

  • 40%–70% adults in the United States
  • Nearly 40%–80% in developing countries

For the majority of people, CMV is not a serious disease.

  • Once infected, CMV remains dormant within the person’s body for life.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Why is CMV an opportunistic infection in an immunocompromised patient?

A
  • Congenital syndrome in neonates (newborns younger than 4 weeks old)
  • Infectious mononucleosis with prolonged fever and hepatitis in young adults
  • Pneumonia in bone marrow recipients
  • Disease syndromes in lung, liver, kidney, and heart transplant recipients
  • Retinitis in AIDS patients
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How is CMV transmitted?

A

Via close, intimate contact with a person who is excreting virus in:

  • Saliva
  • Urine
  • Other bodily fluids

It can be transmitted:

  • Sexually
  • Through breast mild
  • Transplanted organs
  • Blood transfusions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the most imporatnt cause of congenital infections?(during childbirth)

A
  • 1%–3% of women in the US contract a primary CMV infection during pregnancy
  • Virus in mother’s blood can cross over the placenta
  • Developing, unborn babies (neonates) are at highest risk for developing complications of CMV infection.
  • Hearing loss
  • Visual impairment
  • Varying degrees of mental retardation
  • Motor problems
  • 80% of babies with congenital CMV infection grow up healthy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is Chronic CMV infection and aging?

A

Persistent CMV infection has been associated with “immune risk phenotype” (IRP)

  • Expansion of dysfunctional CD8 T cell specific for CMV
  • High CD8 and low CD4 T cell counts
  • Poor overall T cell responses

IRP in older adults linked to:

  • Increased susceptibility to infectious disease
  • Reduced responsiveness to vaccination
  • 2-4 year decrease in survival

Persistent CMV infection has also been associated with low-grade chronic inflammation in the aged overactive innate immunity

  • overproduction of inflammatory cytokines

Associated with frailty and age-associated disease:

  • Alxheimer’s disease
  • Autoimmunity )rheumatoid arhritis; diabetes
  • Cardiovascular disease
  • Cancers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is Epstein-Barr Virus (EBV)?

A
  • Causes 79% of infectious mononucleosis cases
  • CMV causes the other 21%
  • Common infection throughout the world
  • Vast majority of EBV infections occur in young children, and are asymptomatic
  • When EBV strikes individuals in their teens or 20s, it generally becomes symptomatic.
  • May be associated with MS lesions (see Virus File 15-2)
  • In developing countries like Africa, EBV infection is associated with Burkitt’s lymphoma (see Lecture 17)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How is EBV transmitted?

A
  • Often referred to as the “kissing disease”
  • Intimate contact with saliva of an infected person
    • Kissing
    • Sharing beverages
    • Sharing eating utensils
  • Incubation period ranges form 4-6weeks
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the symptoms of Infectious mononucleosis?

A
  • Sore throat
  • Fever
  • Swollen lymph glands
  • malaise
  • Enlarged spleen
  • Enlarged liver
  • Heart problems
  • Central nervous system (CNS) problems (rare)
  • Symptoms usually resolve within a month or two.
  • EBV remains latent in the throat and blood for the rest of a person’s life.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is HHV-6 and HHV-7?

A
  • HHV-6 was isolated from T-cell cultures derived from the blood of AIDS patients.
  • HHV-7 was isolated from CD4+ T cells of a healthy person.
  • Both can infect and kill CD4+ T cells like HIV.
  • Both have been associated with exanthum subitum (“sudden rash”) and infantile fevers and seizures.
  • But most cases are due to HHV-6.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is HHV-6?

A
  • HHV-6 infects nearly all humans by the age of 2
  • Two distince types of HHV-6
    • HHV-6A
    • HHV-6B - causes sixth disease
  • HHV-6 may play a role in multiple sclerosis
23
Q

What is sixth disease?

A
  • Also called Roseloa
  • Most common in those aged 6 months-1 year
  • Incubation period of 5-15 days
    • High fever
    • Pinkish-red skin rash that starts on torso and spreads to extremities and face
    • Rash last hours to 2-3 days
    • Febrile seizures (rare)
24
Q

What is Kaposi’s Sarcoma-Associated Virus?

A
  • KSHV DNA detected in all Kaposi’s sarcomas (see Lecture 17)
  • Aggressive pigmented sarcoma of the skin
    • Known as a skin cancer of elderly men of Mediterranean descent
    • Kaposi’s sarcoma was one of the earliest manifestations of AIDS (1980).
  • Primary infection by KSHV not described
    • Asymptomatic or unrecognized
    • Self-limiting
  • Transmitted largely by saliva
    • also blood and maybe organs
  • Diagnosis easily confirmed by biopsy
25
Q

What are the therapies used to treat Kaposi’s Sarcoma?

A
  • Antiviral drugs are effective against lytic stage of infection
  • none effective during latency
  • Most KSHV- infected cells are latently infected
26
Q

What is Herpes B (Herpes virus Simiae or Monkey B virus)?

A
  • Commonly infects macaques (a type of monkey used extensively in biomedical research)
  • Most macaques carry herpes B infection through direct contact with other macaques (bites, scratches, fomites (e.g., cage scratch)
  • 1932 First human case of herpes B
  • Researcher bitten by an apparently healthy macaque
  • Died 15 days later of encephalomyelitis
27
Q

What is Herpes B infection?

A
  • Incubation period: few days to a month
  • Numbness and sometimes vesicles or ulcers occur at the exposure site.
  • Symptoms
    • Flu-like: fever, muscle aches, malaise, headache
    • Variable symptoms: nausea, vomiting, abdominal pain, hiccups
    • Neurological symptoms when the infection spreads to CNS
  • Most patients with neurological symptoms die, even with antiviral therapy and supportive care.
28
Q

What are the statistics of Herpes B vital stats?

A
  • Only 40 cases have been reported.
  • Majority occurred in the 1950s and 1960s during the production of poliovirus vaccines.
  • Before antiviral therapy was available, this virus was a serious zoonotic threat to people who came in contact with macaques.
  • Herpes B is still prevalent in free-ranging macaques native to Southeast Asia.
  • Free-ranging macaques are a tourist attraction and humans are at risk of contact with infected animals.

Risk is low but death rate is high.

29
Q

What is the herpesvirus envelope?

A

Fragile and easily disrupted by heat, desiccation, 70% alcohol, soap, and detergents

The envelope is extremely sensitive to damage; the virus is usually transmitted by direct contact with the mucosal surfaces or secretions of an infected person (e.g., lips, genitals).

Herpesviruses dry out and become damaged when exposed to air, so it cannot be transmitted by toilet seats or other inanimate objects—a common misconception.

30
Q

What is Hepesvirus Life Cycle?

A

Virus Strucutre and Classes of Herpesviruses

  • Large (150-300nm in diameter)
  • Enveloped (obtained via a double envelopment process)
  • Envelope surrouds icosahedral capsid
  • Pleomorphic particles?
31
Q

What is the hepes virus envelope?

A

Fragile and easily disrupted by heat, desiccation, 70% alcohol, soap, and detergents

The envelope is extremely sensitive to damage; the virus is usually transmitted by direct contact with the mucosal surfaces or secretions of an infected person (e.g., lips, genitals).

Herpesviruses dry out and become damaged when exposed to air, so it cannot be transmitted by toilet seats or other inanimate objects—a common misconception.

32
Q

What is the Hepesvirus Nucleocapsid and the genome?

A
  • Linear dsDNA genome
  • Large genome 125–230 kb in length
  • Herpesvirus virion consists of more than 30 virally encoded proteins.
  • Viral envelope also contains cellular proteins.
  • Capsid that surrounds the dsDNA genome is called an amorphous proteinaceous tegument.
  • Contains at least 8 virally-encoded proteins
  • Initiation of replication
33
Q

What are the three subfamilies of herpesviridae?

A

Subfamilies distinguished by viral latency (cell type) and characteristics of growth in cell culture

34
Q

What is involved in herpesvirus entry and uncoating?

A
  • Herpesviruses attach to the cells of the epidermis or dermis of the skin.
  • Entry occurs through multiple cell-surface receptors and proteins located on the surface of the virion.
  • Binding receptors and entry receptors
  • The viral envelope contains more than a dozen viral integral membrane glycoproteins but only 5 of HSV participate in entry:
  • gB, gC, gD, gH, and gL
35
Q

What are the herpesvirus Entry receptors?

A

Attachment to glycosaminoglycan chains on cells

Heparan sulfate is the preferred binding receptor

36
Q

More on HSV uncoating?

A
  • Nucleocapsid is released into cytoplasm
  • Some tegument proteins remain in cytoplasm
  • Virion host shutoff (vhs) tegument protein plays a role in cellular mRNA degradation, consequently, viral mRNAs accumulate in the cytoplasm and are preferentially translated
  • Other tegument proteins are transported to the nucleus
  • VP16: binds to viral DNA and activates transcription
37
Q

What is the replication?

A

Upon entry, the virus proceeds in one of two possible pathways:

  1. Productive, lytic infection
  2. Latent infection
38
Q

What is productive lytic infection?

A

After uncoating, the viral genome in the nucleus circularizes and is transcribed by cellular DNA dependent RNA polymerase.

  • Viral UL9 protein binds to 1 of 3 possible origins (ORI) and unwinds DNA with help from viral ICP8 protein
  • Helicase/primase complex (UL5, UL8, UL52) synthesizes RNA primers
  • UL30 (viral DNA polymerase) with UL42 binds to the RNA primers and starts DNA synthesis
  • Rolling circle replication
39
Q

What are the hallmarks of herpesvirus genomes?

A
  • Encode enzymes required to increase the pool of nucleotides in a cell and to replicate the viral genome.
    • Thymidine kinase
    • Ribonucleotide reductase
    • Uracil DNA glycosylase (DNA repair)
    • Deoxyuridine triphosphatase
  • These enzymes are good targets for antiviral therapy.
  • About 50% of HSV-1 and HSV-2 genes encode regulatory proteins involved in latency and evading the host immune system (e.g., virokines).
40
Q

What are the transcription properties?

A
  • Transcription is temporally and sequentially regulated in both herpesvirus and poxvirus life cycles.
  • Poxviruses: early, intermediate, late gene expression
  • Herpesviruses: early (alpha), intermediate (beta), late (gamma) gene expression

Like poxivirues

41
Q

Describe herpesvirues transcription.

A
  • Herpesvirus VP16 activates transcription of the alpha genes.
  • The beta genes encode DNA replication and additional viral transcription factors.
  • The gamma genes encode the late structural proteins of the virion that are produced after viral genome replication occurs.
  • Synthesized gamma proteins are transported to the nucleus, where capsid assembly begins.
42
Q

What is involved in Viral membrane formation?

A
  • Occurs by a double envelopment process
  • The viral capsid is enveloped by the nuclear membrane as it translocates the nucleocapsid to the cytoplasm of the cell.
  • The nucleocapsid then buds through the Golgi-derived vesicles and the cellular plasma membrane and cell lysis occurs.
43
Q

What is involved in Viral Replication and Latency?

A

HSV-1 and HSV-2 establish life-long latency in sensory neurons.
Persist as an episome
During latency, a limited number of viral genes are expressed. These are called latency associated transcripts (LATS).
No replication means viral particles are not detected during latency.
The virus hides for months or years until it is reactivated.
Once HSV-1, HSV-2, or VZV is reactivated, it travels the nerve pathway to the surface of the skin.

44
Q

What are the antivirals and treatments of herpesvirus infections?

A

Most comonly prescribed drug is acyclovir

  • Guanosine analog (ACG)
  • Relatively nontoxic
  • Can be used for long-term prophylaxis
  • Can be administered topically to the skin or eye, intravenous or orally.
45
Q

What is the Acyclovir Structure?

A
  • Acyclovir is converted 200× more efficiently to ACG-monophosphate by the herpesvirus thymidine kinase
  • Acts as a chain terminator
46
Q

How does diet play a role in controling infections?

A
  • Research and herpesvirus remission
  • HSV virus proteins synthesized in infected cells contain more arginine than lysine.
  • Foods high in l-lysine may help control HSV outbreaks.
  • Foods high in l-arginine may cause HSV outbreaks.
  • High doses are not recommended.
47
Q

What are the vaccines for chicken pox and other herpes vaccines?

A

Chickenpox vaccine is a live attenuated Oka strain

  • Oka strain isolated from an otherwise healthy 3- year-old Japanese boy (whose family name was Oka) who had an acute case of chickenpox
  • Licensed as Varivax Oka/Merck by the FDA in 1995 for use in the United States

Recommendations

  • One dose between 12 and 18 months of age
  • If the child has not had chickenpox or the vaccine, and is age 13+: two doses, 4–8 weeks apart
48
Q

What are the unanticipated results of the chickenpox vaccine?

A

Breakthrough varicella

  • Wild-type virus that causes mild form of chickenpox (on average a max of 50 lesions or less
  • Occurs in 0.3% to 3.8% of vaccinees
  • More common in the U.S. than in Japan
49
Q

Will the chickenpox vaccines prevent shingles?

A
  • Results of Dept. of Veteran Affairs Shingles Prevention Study: Varivax vaccine reduced shingles cases by 51.3%
  • Zostavax (Merck) was approved by the FDA in 2011 to reduce shingles in people 50+ years old.
  • Each dose contains 14× more live virus than Varivax
  • Exhaustive study determined that vaccination with Zostavax reduced the risk of developing shingles by nearly 70% in adults aged 50–59
50
Q

What are other herpes virus vaccines in the pipeline?

A

Developing a CMV vaccine is a top priority for several reasons:

  • CMV infection is a major disease of the immune compromised
  • CMV is a concern during solid organ transplantation
  • CMV infection is the leading cause of inner ear hearing loss and nervous system damage in children.
51
Q

What is HSV as an attractive vector?

A
  • HSV can replicate in neurons and glia.
  • HSV DNA is easy to manipulate (can carry extra genes).
  • HSV is neurovirulent and would need to be engineered to replicate in a dividing tumor but not in surrounding healthy tissue cells of the CNS.Recombinant HSVs are being engineered to be safe vectors for glioma treatment.
52
Q

What is the use of genetically engineered HSV to treat brain tumors?

A

Pateints with malignant gliomas are idea candidates for novel molecular-based therapies beacuse:

  • Metastases are rare.
  • MRI studies are available to monitor the outcome.
  • Viruses provide a delivery technique that can target the tumor.
53
Q

Does EPV play a role in development of multiiple sclerosis?

A
  • Herpesviruses are ubiquitous in nature and closely adapted to their hosts.
  • Once infected, herpesvirus live in their host for life (latent) and can be reactivated.
  • Evidence of association between EBV infection and autoimmune diseases (including MS).
  • The problem with all of these studies is that herpesviruses correlate with everything and uninfected control patients are difficult to find in significant numbers.
54
Q

What is herpesviru latency and symbiosis?

A

Experimental data show that mice latently infected with herpesviruses were resistant to some bacterial infections

  • Chronic stimulation of innate immunity
  • Increased circulating levels of cytokines

Symbiosis- benefit to both virus and host?

  • Unclear whether this is true in humans
  • Is protection transient or lifelong?

Virology (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions