DNA Viruses Flashcards Preview

HMS Immunology and Microbiology > DNA Viruses > Flashcards

Flashcards in DNA Viruses Deck (43)
Loading flashcards...
1
Q

“Shock and kill” method for treating latent virus

A

Shock = give drugs to reactivate viral transcription

Kill = sensitize against the virus and destroy cells it appears in

This method is currently under development and is believed to be the future of antiviral treatment for latent viruses (HIV, Herpesviruses, HPV, Varicella Zoster, Hep B, etc.)

2
Q

Herpesviruses are divided into. . .

A

α Herpesviruses

β Herpesviruses

γ Herpesviruses

3
Q

α Herpesviruses (list)

A

Herpes simplex virus-1

Herpes simplex virus-2

Varicella-zoster virus

4
Q

β Herpesviruses

A

Cytomegalovirus

Human herpesvirus-6

Human herpesvirus-7

5
Q

γ Herpesviruses

A

Epstein-Bar virus (the kissing virus)

Human herpesvirus-8

6
Q

Herpes virus viral taxonomy

A

Encapsulated linear dsDNA, icosahedral nucleoplasmid

7
Q

An important biological characteristic of all herpesviruses is the capacity to establish ____.

A

An important biological characteristic of all herpesviruses is the capacity to establish lifelong latent infections

8
Q

Herpesviruses are ___.

A

Herpesviruses are fragile

They are and susceptible to drying and inactivation by heat, mild detergent, and solvents. Their susceptibility is imposed by their membrane envelope

9
Q

VZV is usually acquired from an infected person by the ____ route.

A

VZV is usually acquired from an infected person by the respiratory route,

but infection by direct contact with vesicular fluid or secretions also can occur

10
Q

Primary disease caused by VZV is ___ contagious

A

Primary disease caused by VZV is highly contagious

11
Q

Chickenpox

A

aka Varicella

systemic febrile disease with mucocutaneous lesions

12
Q

Complications of chickenpox

A

Cerebellar ataxia in otherwise healthy children and encephalitis in immunocompromised persons.

13
Q

How varicella diseminates

A

Cells of the lymphatic system are infected at the site of entry in the respiratory tract. Spread of virus-infected leukocytes throughout the lymphatic system induces cytokine responses that result in fever, malaise, and headache. Circulating leukocytes transmit the virus to epithelial cells of the skin and mucosa, and the characteristic lesions of chickenpox occur.

ie, primary infection in lung, secondary in epithelia via lymphatics

14
Q

Latent infections of varicella are established in. . .

A

Latent infections of varicella are established in peripheral ganglia

15
Q

Zoster

A

aka Shingles

similar to the vesicular lesions of chickenpox except that they are clustered on skin along the dermatome innervated by the nerve from which VZV was reactivated. Associated with severe pain, may be disseminated in immunocompromised individuals, and likelihood of reactivation increases linearly with age.

16
Q

Gene regulation in varicella zoster

A

During viral replication, immediate-early genes are transcribed with the assistance of transcription factors carried in the virus. Proteins encoded by immediate-early genes activate expression of about a dozen early genes whose protein products are required to replicate the viral DNA. Next, the late genes are expressed. Late genes encode proteins that assemble and compose the progeny virions.

17
Q

Varicella zoster lifecycle

A
18
Q

The membrane around a varicella zoster virion comes from. . .

A

the trans-Golgi network vesicles of a previous host cell.

19
Q

In latently infected cells, the varicella zoster genome. . .

A

. . . persists as an episome within the nucleus of the infected host cell, with minimal transcription of viral genes.

20
Q

Diagnosing varicella zoster

A

The patient’s clinical presentation and history are usually sufficient to lead to a diagnosis. To confirm, the presence of virus in active lesions can be detected by polymerase chain reaction or immunoassays.

VZV is difficult to propagate in cell culture and so this is an insensitive test.

21
Q

When are antiherpesvirus medications indicated for infected individuals?

A

Importantly, NOT for childhood varicella in an otherwise healthy child.

However, antiviral therapy is indicated in severe cases of chickenpox, chickenpox in immunosuppressed children or adults, shingles, and VZV infections associated with meningitis, encephalitis, or any other neurological manifestation.

22
Q

Antiherpesvirus medications cannot. . .

A

. . .effect a “cure”, because they does not prevent entry of virus into neurons and cannot eliminate latent viral genomes.

23
Q

Acyclovir

A

Inhibits HSV and VZV polymerases. Must first be phosphorylated by a virus-derived thymidine kinase, then twice by host kinases, to generate its active form.

24
Q

Valacyclovir

A

prodrug of acyclovir has improved oral bioavailability

25
Q

Prevention of varicella zoster virus

A

A live, attenuated VZV vaccine prevents chickenpox with 80% efficacy overall, and 99% efficacy in preventing severe disease.

People with chickenpox should be isolated and vaccination offered to family members or other contacts. Virus can be transmitted via the aerosol route.

26
Q

Infection with ____ by adulthood is nearly universal in the developing world.

A

Infection with Epstein-Barr virus by adulthood is nearly universal in the developing world.

27
Q

Transmission of Epstein-Barr virus

A

EBV spreads most commonly through bodily fluids, especially saliva. However, EBV can also spread through blood and semen during sexual contact, blood transfusions, and organ transplantations. EBV can be spread by using objects, such as a toothbrush or drinking glass, that an infected person recently used.

Intermittent excretion of EBV on mucosal surfaces in the absence of clinical symptoms is common

28
Q

EBV-mediated disease

A

Primary infection in young adults can be associated with an acute mononucleosis syndrome that consists of low-grade fever, fatigue, pharyngitis, cervical lymphadenopathy, splenomegaly, and peripheral blood monocytosis with atypical or reactive lymphocytes.

29
Q

Posttransplant lymphoproliferative disease

A

Following reactivation, lytic EBV infection in an immunosuppressed transplant recipient can induce lymphoproliferation.

In its most benign form, the virus produces an acute mononucleosis-like syndrome with lymphoid proliferation. Untreated, this initially benign lymphoproliferation can evolve into an oligoclonal neoplasm that in some cases subsequently develops into a lymphoma.

30
Q

EBV and Lymphomas

A

EBV is associated with Hodgkin lymphoma, Burkitt lymphoma, nasopharyngeal carcinoma, and more recently gastric carcinoma.

31
Q

EBV is present in about ____% of Hodgkin lymphomas.

A

EBV is present in about 40% of Hodgkin lymphomas.

32
Q

Burkitt lymphoma

A

IGH promoter, c-Myc sequence.

The mechanism by which EBV contributes to neoplasia in these cells is poorly understood

33
Q

Nasopharyngeal carcinoma

A

Endemic in southern China and some parts of Africa. EBV is consistently found in the cancerous cells, and these patients have high levels of antibodies to some EBV proteins. Viral latent membrane protein 1 (LMP-1) in the cancerous cells activates the NF-kB pathway.

This contributes to neoplasia, although the precise mechanism by this occurs is not well understood.

34
Q

EBV-mediated damage

A
  • initially infects oropharyngeal epithelial cells, and then spreads to nearby B cells in the tonsils and adenoids.
  • At some point switches from latency to lytic within B cells
  • In most infected B-cells, EBV establishes latent infection
  • Minimal number of viral genes expressed in most cells to maintain viral reservoire
  • Splenomegaly and lymphadenopathy from intense lymphocyte proliferation (B cells, CD8 cells)
  • Fever, malaise from large amounts of cytokine produced by the response
35
Q

Regulation of genes throughout EBV’s lifecycle

A

In initial phases, viral genes such as Epstein-Barr nuclear antigen-1 are expressed to insure maintenance and partitioning of the viral episome. Expression of the latent membrane proteins, LMP1 and LMP2a, provides growth signals to infected cells that drive cellular proliferation.

Reactivation of EBV from latency occurs sporadically.

36
Q

Mononucleosis occurs ___ during EBV infection

A

Mononucleosis occurs early during EBV infection

associated with the strong host immune system response to initial infection. Large numbers of activated CD8+ cytotoxic T-lymphocytes specific for EBV are generated. These are seen as “atypical lymphocytes” in the peripheral blood film, and are the mononuclear cells from which this illness takes its name.

Activation and proliferation of these lymphocytes is what induces splenomegaly and lymphadenopathy.

37
Q

Diagnosing EBV

A
  1. Seroconversion (IgM measurement)
  2. Monospot” test for clonal plasma cells / monoclonal antibody production
  3. PCR is sensitive and specific for secondary infection or progressive primary, but not resolving primary infections.
38
Q

Treatment of EBV

A

EBV infections in normal immunocompetent individuals are almost always self-limited and thus, rarely, if ever, require treatment.

Treatment of EBV infections in the immunocompromised host is difficult. Although acyclovir and related gancyclovir have some activity against EBV, treatment of PTLD in EBV-infected transplant recipients with these agents has minimal, if any, efficacy.

39
Q

Upon reactivation, a herpesvirus. . .

A

Upon reactivation, a herpesvirus mediates lytic infection of the same cell in which it was previously latent.

40
Q

____ are the only DNA viruses with their own encoded DNA-dependent RNA polymerase.

A

Poxviridae are the only DNA viruses with their own encoded DNA-dependent RNA polymerase.

41
Q

___ all utilize their own DNA polymerase rather than the cell’s.

A

Hepadnaviridae, adenoviridae, herpesviridae, and poxviridae all utilize their own DNA polymerase rather than the cell’s.

42
Q

Bell’s palsy

A

Palsy of the facial nerve, often unilateral.

Suggestive for α-herpesvirus infection in the absence of trauma.

43
Q

In latent viral episomes, DNA is ____.

A

In latent episomes, DNA is epigenetically silenced.

In HSV, this is mediated by LAT.