Viral Infxn Of The Blood

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Herpesviridae

Back 1

Linear dsDNA then circular during infxn
Enveloped icosahedral
Replicate in the NUCLEUS
Gain MEMBRANE from BUDDING of the Nucleus
Latency (secretory/lymphoid/kidney cells)

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Herpesviridae Replication

ADD

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Translation and gene expression is temporal
Immediate -> regulatory for shurring of host cell protein synth and destruction of host cell mRNA and DNA
Early-> Replication of Viral Dna

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Epstein Barre Virus

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90% of pop. exposed by age 30
Gamma Herpesvirus
Young Children asymptomatic
Adolescents --> Kissing disease
cause of HETEROPHILE positive IM

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EBV Transmission

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Saliva --> to epithelial cells of oropharynx
Recepter mediated attach (CD21/CR2 + co-MHCII-receptor)

Latent infxn in Memory B-cells
Replication in epithelial cells of oral cavity

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EBV Pathogenesis

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Mitogen activates B cells and reactive T-cells
POLYCLONAL lymphocyte activation
Production of ABs to Host and Viral proteins

Atypical T-Cells (activated CTLs)

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Infectious Mononucleiosis Sx

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PHARYNGITIS (sore throat) + Tonsilitis w/ EXUDATE
Flu like Sx and LAD AND MALAISE
Fatigue
LAD
SPLENOmegaly (week 3-4)

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Heterophile Antibodies

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IgM isotype
affinty for sheep horse cow RBCS
[agglutination is a positive test (MONOSPOT)]
AB can develop against other Ag such as Ampicillin
Hypersensitivity rxn (not a penicillin allergy)

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Test for Heterophile Antibodies

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MONOspot test (heterophile AB test)
(Agglutination is a positive test)
Lymphocytosis w/ > 10% Atypical CTLs

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Ampicillin Hypersensitivity Rxn to Ampicillin

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Not necessarily an allergy to penicillin
Macular Rash
From non specific AB forming against ampicillin

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Serologic Antibodies for EBV

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VCA - viral capside
EA - early Ag

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Lymphoproliferative Disease

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Oncogenic Result of EBV
Burkitt Lymphoma (c-myc gene translocation)
Co-factor infxn w/ MALARIA

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Betaherpesviridae

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Cytomegalovirus
Enlargement of cells
Common ~80-100%

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Transmission of CMV

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Breast milk, salvia, feces, urine, cervical secretions, semen, blood

Sexually Active Young Adults

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Cell Morphology of CMV

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LARGE Intranuclear Inclusions w/ HALO (Owls eye)
Smaller cytoplasmic Inclusions
Cells 2-4 times larger than normal

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CMV and Infectious Mononucleosis

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Syndrome Similar to EBV
>10% atypical lymphocytes
HETEROPHILE ANTIBODY NEGATIVE

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Others affected by CMV

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TRANSPLANTS patients can receive it from latent tissue --> Graft Loss
FETUS --> cytomegalic inclusion disease
Immunocompromised --> Retinitis, GI issues, Meningoencephalitis after initial NIGHT SWEATS, flu like sx, arthralgias, myalgias

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Dx of CMV

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Culturing (fibroblast monolayers or shell vials)
Immunofluorescence
PCR
Histological Staining
"Owl's Eye Stain"

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EBV associated with what carcinoma

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Nasopharyngeal
Burkitts Lymphoma

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Retroviridae

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RNA-->DNA-->RNA-->Peptide
Enveloped ssRNA
Virion carries RT which along with integrase incorporates Viral DNA into Host Genome

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HIV affect on the immune system

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Altering/damaging the CD4+ T cells
CD4:CD8 from 2:1 to 1:2
Synctium Formation (SOME)
non neutralizing Antibodies
WITHOUT CD4 --> CTLs and B cells dont work properly

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Retroviridae Pathogenesis

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Mucoase -> lamina propria -> local CD4 -> drainign lymph nodes -> other lymphoid tissues
Blood Infxn --> circulation to spleen

in Nodes the viremia can become systemic (acute HIV - Symptomatic)

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Gut Associated Lymphoid Tissue (GALT)

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very important in HIV gaining a foothold
initial viral replication

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When does HIV move to AIDs

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When CD4+ <200 cells/ul

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Sx of Acute HIV

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Flu Like Sx
Fever (38-40°C)
Wt Loss
Malaise, HA, Neuropathy
Sores and Thrush of mouth
LAD
Rash (trunk, neck and face)
Myalgia
Hepato/Splenomegaly

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HIV1 sub groups

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N, M , O

Clades of M A-J

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Infxn of HIV1/HIV2

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HIV 1 more virulent and faster onset

HIV 2 differes in several genes

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Why Diversity in HIV

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low fidelity of Reverse Transcriptase
high mutation rate
Selection pressure from CTLs and ABs on ENV
but RT is highly Conserved

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HIV Structure

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Enveloped
Glyco proteins (GP120 and transmembrane gp41)
capsid with p24 proteins
+ssRNA 2 copies
Reverse Transcriptase
Integrase
Transfer RNA

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Genome Structure of HIV

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ssRNA (2 strands)
9 genes (GAG POL ENV and 6 regulatory)
Reg. Regions:
LTR at 5' and 3' ends (important fot integration)
5' regulates initiation of RNA transc
3' regulates termination and polyadenylation

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4 main genes of HIV

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GAG - capsid
PRO - protease
POL - RT, Integrase
ENV - surface (GP120) and envelope (gp41) proteins

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ENV Gene

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embeded

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Protease activity

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Used to cut initial synthesized proteins into fxnal active proteins

GAG into 3-4 proteins
ENV into 2 proteins

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Attachment of HIV

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Attachment (GP120/41 with CD40/coreceptor)
Entry - fusion with cell membrane (gp41 assisted)
Uncoating
Replication
Assembly
Release

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Acute HIV definition

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High levels of Plasma HIV RNA
Negative Anti-HIV 1 ELISA
Negative Western Blot

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Dx of Acute HIV

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4th Gen EIA for p24 Ag (less sensitivity/specificity)

Based on detection of HIV RNA:
Branched Chain DNA, PCR, GenProbe
100% specificity and sensitivity

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Differential Dx for Acute HIV

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Infectious Mono
CMV
Syphilis
Rubella
Toxoplasmosis
Viral Hepatitis

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Pneumocystis Pneumonia (PCP) and Sx

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Fungal invasion
Caused a lot of the early AIDs deaths

Triad
Dry Cough, Subfebrile temp, and Dyspnea on Exertion

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Bacterial Pneumonia Sx

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Productive cough
High Fever
Less common dyspnea

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Common Complications associated w/ HIV Infxn

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Pneumocystis Pneumonia (fungal)
Candidiasis (thrush)
MAC (mycobacterium avian complex) - Abscess/fistula
Cryptococcosis (CNS sx - encephalitis)

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How long after Infxn does Acute HIV evolve Sx

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2-4 weeks

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Tx of PCP

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Co-Trimoxazole +

Clindamycin + Primaquine

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Tx of Candidiasis

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Mild: Topical Amphotericin B

Severe: Fluconazole

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Tx of MAC

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Macrolides

Azithromycin or Clarithromycin + ethambutol

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Tx of Cryptococcosis

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Amphotericin B (for 14 days)
Oral flucytosine

Fluconazole (for consolidation and maintenance)

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Dx of Cryptococcosis

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Lumbar Puncture
CT scan
Fundoscopy

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CMV vs EBV Sx

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CMV does not have exudative pharyngitis
OR LAD

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Is HIV oncogenic

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Lentivirinae is NON-oncogenic

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Flucytosine Sd Fx

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Bone Marrow Suppression

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Fluconazole

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GI Issues
hepatotoxic

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Amphotericin B

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Renal Toxicity
Electrolyte abnormality