CMV, EBV, and HIV Flashcards
CID
“Cytomegalic inclusion disease”
- Primary CMV infxn of the mother spreads to the fetus in utero
- Targets the visceral organs (***chorioretinopathy, liver disease, microencephaly, TTP)
CMV infection pathways
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)
CMV Treatment
Ganciclovir
or
Cidofovir (CMV retinitis)
*CMV can prevent MHC-I expression limiting natural response
EBV interactions w/ Cells
- 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
- Latent infections: Viral genome circularizes to form a plasmid and replicates in tandem w/ the cell; only EBNA and Latent proteins formed
- B-cell immortalization: LMPs stimulate replication of B-cells and the virus
Infectious Mononucleosis
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
HHV7
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
HHV8
Causes Kaposi’s Sarcoma; infects B-cells and slows their apoptosis by producing IL-6 analogs
CMV Characteristics
- 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
HTLV-1
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
Env (HIV proteins)
Encode for glycoprotein spikes on the envelope
-Includes gp160 (and gp120, gp41)
TAT (HIV proteins)
Transcription Transactivator
REV (HIV proteins)
Regulates transport of the virus out of the nucleus; also encodes for mRNA splicing
NEF (HIV protein)
Diminishes cellular CD4 and MHCI class expression
**Necessary in order to achieve high viral load
VIF (HIV protein)
Promotes viral assembly and blocks the fnxn of APOBEC-3G in the cell that is normally an antiviral
VPU (HIV protein)
Enhances the release of the virus from the cell and decreases CD4 expression
VPR
Arrests affected cells in the G2 phase of the cell cycle (best for replication) and enhances the transport of the virus into the nucleus
HIV Structure
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
HIV mRNAs that are spliced twice
TAT and REV
*TAT can be released by HIV-infected cells to serve as a transcription activator for HHV-8 (Kaposi’s Sarcomas)
HIV Diagnosis
ELISA for HIV-antibodies (anti-gp120, 41, 24)
Confirm w/ Western Blot
*Now have screening finger-sticks/oral test and provides rapid result
Opportunistic Infections in CD4
CD4 > 200 PCP
-Treat w/ Bactrim
CD4 > 150 Toxoplasmosis
-Treat w/ Bactrim
CD4 > 50 MAC and CMV
-Azithromycin and Ganciclovir
Complera
Rilpirivine + emtricitibine + tenofovir
*Only works if viral load is
Stribild
Used on treatment naive pts.
Contains 4 drugs
Cobicistat (Tybost)
Used w/ elvitegravir as a “boosting agent”
-inhibits CYP3A ➡️➡️ increased half life of other drugs
Part of the “quad pill,” Stribild
Maraviroc
Binds to CCR5 inhibiting entry of HIV into the cell
-Can only be used on pts. w/ M-tropic virus
Enfurvitide
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
Efavirenz
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
Nevirapine
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
Abacavir
NRTI (needs phosphorylation to inhibit RT)
MUST SCREEN for anti-HLA ab (HLAB5701) before initiating therapy
Tenofovir
NRTI; allows continued efficacy against HIV strains that have developed some resistance
ADR: Lactic acidosis; steatosis; BM suppression; exacerbation of Hep B
Zidovudine
NRTI w/ severe BM suppression
-Also has lipoatrophy, myoatrophy, and insulin resistance
Elvitagravir (and anything w/ -gravir)
Integrase inhibitor; inhibition of viral DNA strand transfer to host DNA
ADR: Pyrexia; CK elevation
Ritonavir
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
Darunavir/Tipranavir
Good for PI-resistant HIV strains
-Can cause rash/hepatotoxicity
HIV Treatment for Pregnant Women
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
Post-exposure HIV prophylaxis
Raltegravir and Truvada
First treatment in
Pre-exposure prophylaxis
Truvada; decreases rate by ~90%
Didanosine
NRTI assoc. w/ pancreatitis and peripheral neuropathy
Raltegravir, Elvitegravir
Integrase inhibitor
Restricted to treatment of multiple drug resistant HIV pts. and is assoc. w/ CPK elevation and pyrexia
HIV Mechanisms for destruction of uninfected T-cells
Activation-induced apoptosis
Non-cytopathic infxn- inflammatory mediators cause pyroptosis
Destruction of immature precursors in the thymus
Formation of syncytia w/ uninfected cells
Latency of HIV
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
Macros and HIV
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
Dendritic Cells in HIV
Initially infected in the and transport the virus to the lymph nodes infecting CD4 cells
B-cells and HIV
Initially undergo hyperplasia and exhibit hypergammaglobulinemia
=»Inability to mount proper immune response leads to increased infxns by encapsulated organisms
Path of HIV Infection
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)
Progressive Multifocal leukoencephalopthy
Opportunistic infection in AIDS pts. cause by human papovavirus
-PJ, CMV, Candida, HSV, Toxoplasmosis, and Cryptococcus other possible infxns
Serology of HIV
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
What tests should you do if you really suspect early HIV?
4th generation test AND RT-PCR at the same time
MYC protooncogene
Activated by EBV to produce Burkitt’s lymphoma in endemic areas
