Unit 4 -Herpesvirus Flashcards

Question

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

Answer 1

* Antiviral drugs are effective against lytic stage of infection * **_none_** effective during latency * Most KSHV- infected cells are latently infected

Answer 2

* 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

Answer 3

* 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.

Answer 4

* 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.

Answer 5

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.

Answer 6

Virus Strucutre and Classes of Herpesviruses * Large (150-300nm in diameter) * Enveloped (obtained via a double envelopment process) * Envelope surrouds icosahedral capsid * Pleomorphic particles?

Answer 7

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.

Answer 8

* 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

Answer 9

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

Answer 10

* 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

Answer 11

Attachment to glycosaminoglycan chains on cells Heparan sulfate is the preferred binding receptor

Answer 12

* 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

Answer 13

Upon entry, the virus proceeds in one of two possible pathways: 1. Productive, lytic infection 2. Latent infection

Answer 14

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

Answer 15

* 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).

Answer 16

* 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

Answer 17

* 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.

Answer 18

* 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.

Answer 19

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.

Answer 20

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.

Answer 21

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

Answer 22

* 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.

Answer 23

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

Answer 24

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

Answer 25

* 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

Answer 26

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.

Answer 27

* 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.

Answer 28

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.

Answer 29

* 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.

Answer 30

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?

Unit 4 -Herpesvirus Flashcards

(54 cards)