CMV, EBV, and HIV Flashcards

1
Q

CID

A

“Cytomegalic inclusion disease”

  • Primary CMV infxn of the mother spreads to the fetus in utero
  • Targets the visceral organs (***chorioretinopathy, liver disease, microencephaly, TTP)
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2
Q

CMV infection pathways

A

Acquire newborn: CMV secreted into the cervix at the last trimester and poses infxn threat

Normal (respiratory): Mostly asymptomatic; heterophile antibody (-)

Post-transplantation: **Big cause of renal transplant failures (takes a couple weeks)

Latent Reactivation: Significant in AIDS pts. (CMV retinitis, esophagitis)

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3
Q

CMV Treatment

A

Ganciclovir

or

Cidofovir (CMV retinitis)

*CMV can prevent MHC-I expression limiting natural response

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4
Q

EBV interactions w/ Cells

A
  1. Replication w/in permissive cells: gp350/220 on the envelope enable attachment of the virus to CD21
    • Also contains EBNA, MA, VCA, and EA proteins
  2. Latent infections: Viral genome circularizes to form a plasmid and replicates in tandem w/ the cell; only EBNA and Latent proteins formed
  3. B-cell immortalization: LMPs stimulate replication of B-cells and the virus
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5
Q

Infectious Mononucleosis

A

Splenomegaly, lymphadenopathy, exudative pharyngitis, Downey cells in PB, alongside B-symptoms

Diagnosis: Monospot test (agglutination=+; occurs due to presence of heterophile antibodies)
-Immunofluorescence; abs to EBNA, MA, VCA, EA

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6
Q

HHV7

A

Causes roseola characterized by a high fever followed by a rash when the fever resides

-HHV6B also causes this w/o as high a fever

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7
Q

HHV8

A

Causes Kaposi’s Sarcoma; infects B-cells and slows their apoptosis by producing IL-6 analogs

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8
Q

CMV Characteristics

A
  • Contains Double-stranded DNA and viral mRNA (most viruses only contain one or the other)
  • Replication occurs in fibroblasts, macros, and epithelial cells for 4-6 weeks before CPE is seen (owl-eye inclusions)
  • Latent infections can be established in monos and virus is spread via lymphs
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9
Q

HTLV-1

A

Causes adult T-cell leukemia and Tropical Spastic Paraparesis (urinary incontinence, trouble walking)

-Transmitted thru cellular material in breast feeding, intrauterine modes, and perinatal routes

Screen: EIA for HTLV-1 abs
Confirmatory: Western Blot

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10
Q

Env (HIV proteins)

A

Encode for glycoprotein spikes on the envelope

-Includes gp160 (and gp120, gp41)

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11
Q

TAT (HIV proteins)

A

Transcription Transactivator

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12
Q

REV (HIV proteins)

A

Regulates transport of the virus out of the nucleus; also encodes for mRNA splicing

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13
Q

NEF (HIV protein)

A

Diminishes cellular CD4 and MHCI class expression

**Necessary in order to achieve high viral load

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14
Q

VIF (HIV protein)

A

Promotes viral assembly and blocks the fnxn of APOBEC-3G in the cell that is normally an antiviral

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15
Q

VPU (HIV protein)

A

Enhances the release of the virus from the cell and decreases CD4 expression

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16
Q

VPR

A

Arrests affected cells in the G2 phase of the cell cycle (best for replication) and enhances the transport of the virus into the nucleus

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17
Q

HIV Structure

A

Consists of two identical RNA genomes held together by tRNA (p9 and p7); housed in a cylindrical capsid containing p24

Envelope contains gp160 (major in M-tropic) and gp120-gp41 (major in T-tropic)

*gp120=»attaches to the cell receptor
gp41=»responsible for cell fusion

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18
Q

HIV mRNAs that are spliced twice

A

TAT and REV

*TAT can be released by HIV-infected cells to serve as a transcription activator for HHV-8 (Kaposi’s Sarcomas)

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19
Q

HIV Diagnosis

A

ELISA for HIV-antibodies (anti-gp120, 41, 24)

Confirm w/ Western Blot

*Now have screening finger-sticks/oral test and provides rapid result

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20
Q

Opportunistic Infections in CD4

A

CD4 > 200 PCP
-Treat w/ Bactrim

CD4 > 150 Toxoplasmosis
-Treat w/ Bactrim

CD4 > 50 MAC and CMV
-Azithromycin and Ganciclovir

21
Q

Complera

A

Rilpirivine + emtricitibine + tenofovir

*Only works if viral load is

22
Q

Stribild

A

Used on treatment naive pts.

Contains 4 drugs

23
Q

Cobicistat (Tybost)

A

Used w/ elvitegravir as a “boosting agent”

-inhibits CYP3A ➡️➡️ increased half life of other drugs

Part of the “quad pill,” Stribild

24
Q

Maraviroc

A

Binds to CCR5 inhibiting entry of HIV into the cell

-Can only be used on pts. w/ M-tropic virus

25
Q

Enfurvitide

A

MOA: Binds to gp41 inhibiting HIV-1 viral fusion w/ the host membrane

*Only HIV Injection drug =» painful nodules @ site of injection; possible allergic rxns too

26
Q

Efavirenz

A

NNRTI that MUST BE used w/ 2 other agents; has a very long half-life so it can lead to only the exposure of one agent to the virus =» possible development of RESISTANCE

  • Severe neurological symptoms including somnolence, dizziness, confusion, abnormal dreams
  • Also has occurrence of rash as with all NNRTIs
27
Q

Nevirapine

A

NNRTI that inhibits RT; must use w/ 2 other agents as w/ what other drug?

*Possible cause of Steven-Johnson Syndrome; frequently causes at least a rash

⭐️⭐️Use w/ CD4 counts >250

28
Q

Abacavir

A

NRTI (needs phosphorylation to inhibit RT)

MUST SCREEN for anti-HLA ab (HLAB5701) before initiating therapy

29
Q

Tenofovir

A

NRTI; allows continued efficacy against HIV strains that have developed some resistance

ADR: Lactic acidosis; steatosis; BM suppression; exacerbation of Hep B

30
Q

Zidovudine

A

NRTI w/ severe BM suppression

-Also has lipoatrophy, myoatrophy, and insulin resistance

31
Q

Elvitagravir (and anything w/ -gravir)

A

Integrase inhibitor; inhibition of viral DNA strand transfer to host DNA

ADR: Pyrexia; CK elevation

32
Q

Ritonavir

A

Protease inhibitor that prevents HIV from cleaving peptides into smaller, fnxnal virions

-**Booster that allows lower doses and pill burden for several antivirals

  • Can also cause parasthesias
  • **ASSOC. W/ Endocrine abnormalities: hyperlipidemia, insulin resistance, osteonecrosis
33
Q

Darunavir/Tipranavir

A

Good for PI-resistant HIV strains

-Can cause rash/hepatotoxicity

34
Q

HIV Treatment for Pregnant Women

A

ART combination: DURING LABOR IV Zidovudine IF HIV RNA >400copies/mL

***Cannot use efavirenz =» severe teratogen that causes neural tube malformation; if after 5-6 weeks, treatment can be continued

=»Do pregnancy test before starting this treatment

**Should even give Zidovudine and nevarapine 6/wks post-partum

35
Q

Post-exposure HIV prophylaxis

A

Raltegravir and Truvada

First treatment in

36
Q

Pre-exposure prophylaxis

A

Truvada; decreases rate by ~90%

37
Q

Didanosine

A

NRTI assoc. w/ pancreatitis and peripheral neuropathy

38
Q

Raltegravir, Elvitegravir

A

Integrase inhibitor

Restricted to treatment of multiple drug resistant HIV pts. and is assoc. w/ CPK elevation and pyrexia

39
Q

HIV Mechanisms for destruction of uninfected T-cells

A

Activation-induced apoptosis

Non-cytopathic infxn- inflammatory mediators cause pyroptosis

Destruction of immature precursors in the thymus

Formation of syncytia w/ uninfected cells

40
Q

Latency of HIV

A

Remains in CD4 cells and macros =» hides here from retroviral therapy

-During latency, decreased CD4 cells also cause: loss of memory, decreased helper fnxn, and decreased cell-mediated immunity

41
Q

Macros and HIV

A

Provide a reservoir and inhibit the fnxns of macrophages

-Also cause infxn of the CNS as monocytes carry the virus to the brain and cause indirect damage

42
Q

Dendritic Cells in HIV

A

Initially infected in the and transport the virus to the lymph nodes infecting CD4 cells

43
Q

B-cells and HIV

A

Initially undergo hyperplasia and exhibit hypergammaglobulinemia

=»Inability to mount proper immune response leads to increased infxns by encapsulated organisms

44
Q

Path of HIV Infection

A

Virus enters thru mucosal epithelia and infects CD4+ cells there; infected DCs transport virus to lymph nodes where replication causes increased viral load

*Seroconversion occurs as a humoral and cell-mediated response occurs (Acute HIV syndrome)

45
Q

Progressive Multifocal leukoencephalopthy

A

Opportunistic infection in AIDS pts. cause by human papovavirus

-PJ, CMV, Candida, HSV, Toxoplasmosis, and Cryptococcus other possible infxns

46
Q

Serology of HIV

A

Abs: Response 6 days- 1 month after initial infxn; antigenemia occurs first (rapid finger stick detects anti-HIV1 and 2 and also p24-Ag)

Viral Load: Used to monitor effectiveness of therapy

ID: Identify p-24 antigen; then the antibodies

-May need to do nucleic acid test for HIV-1 if First part is positive and second is negative

47
Q

What tests should you do if you really suspect early HIV?

A

4th generation test AND RT-PCR at the same time

48
Q

MYC protooncogene

A

Activated by EBV to produce Burkitt’s lymphoma in endemic areas