Micro - Virology (HIV) Flashcards
Pg. 164-166 Sections include: HIV HIV diagnosis Time course of HIV infection Common diseases of HIV-positive adults
Describe the HIV genome. Include ploidy, type(s) and number of molecules.
Diploid genome (2 molecules of RNA)
What are the structural genes of HIV?
(1) env (2) gag (3) pol
What product(s) does the HIV structural gene env encode?
Env codes for gp160, which is cleaved to form envelope proteins gp120 and gp41
In what HIV structural gene is gp120 coded? What is the role of gp120?
Env (which directly encodes gp160, which is later cleaved to gp120 and gp41); Docking glycoprotein for Attachment to host CD4+ T cell
In what HIV structural gene is gp41 coded? What is the role of gp41?
Env (which directly encodes gp160, which is later cleaved to gp120 and gp41); Transmembrane glycoprotein for Fusion and entry
What product(s) does the HIV structural gene gag encode? What is the role of this/these product(s)?
p24; Capsid protein
In what HIV structural gene is p24 coded? What is the role of p24?
gag; Capsid protein
With what product(s) is the HIV structural gene pol associated?
(1) Reverse transcriptase (2) Aspartate protease (3) Integrase
What role does reverse transcriptase play?
Synthesizes dsDNA from RNA (which permits the dsDNA to later be integrated into the host genome)
What is the fate of the dsDNA synthesized from RNA by reverse transcriptase?
Integrated into host genome
What are the envelope proteins of HIV? How are they acquired?
gp120 & gp41; Acquired through budding from host cell plasma membrane
Where does HIV virus bind in its host? Clarify binding in early versus late infection.
Virus binds CCR5 (early) or CXCR4 (late) co-receptor and CD4 on T-cells; Also bind CCR5 and CD4 on macrophages
What does homozygous CCR5 mutation cause? What does heterozygous CCR5 mutation cause?
Immunity; Slower course
How is HIV diagnosed? Compare and contrast the tests used.
Presumptive diagnosis made with ELISA (sensitive, high false-positive rate and low threshold, RULE OUT test); Positive results are then confirmed with Western blot assay (specific, high false-negative rate and high threshold, RULE IN test)
What do HIV PCR/viral load tests determine? What is the clinical relevance of this measure?
Amount of viral RNA in the plasma; (1) HIgh viral load associated with poor prognosis (2) Viral load used to monitor effect of drug therapy
What is a normal CD4+ cell count? What CD4+ cell count defines an AIDS diagnosis?
500-1500 cells/mm^3; Less than or equal to 200 cells/mm^3
What are ways to define an AIDS diagnosis?
(1) Less than or equal to 200 CD4+ cells/mm^3 (normal: 500-1500) (2) HIV positive with AIDS-defining condtion (e.g., Pneumocystis pneumonia, or PCP) (3) HIV positive with CD4/CD8 ratio < 1.5
What do the Elisa/Western Blot HIV tests detect? What kind of false readings are seen with these tests, and in what circumstances?
Antibodies to viral proteins; Often are fasely negative in the first 1-2 months of HIV infection & falsely positive initially in babies born to infected mothers (anti-gp120 crosses placenta)
What are the four stages of untreated HIV infection? What is a good way to remember this?
Four stages of infection: (1) Flu-like (acute) (2) Feeling fine (latent) (3) Falling count (4) Final crisis; All F’s
What significant event happens during the latent phase of HIV, and where?
Virus replicates in the lymph nodes
Draw the structure of HIV and its contents.
See illustration on pg. 164 in First Aid
What initially occurs upon HIV infection?
Acute phase = (1) Acute HIV syndrome (2) Wide dissemination of virus (3) Seeding of lymphoid organs
What CD4+ T cell count is considered to be immunocompromised? Again, what is the AIDS-defining CD4+ T cell count?
Less than 400 CD4+ cells/mm^3; Less than 200 CD4+ cells/mm^3
Draw the time course of HIV infection as a dual graph of CD4+ T cells/mm^3 and HIV RNA copies/mL as separate y axes & months to years on the x axis. Label the following based on the time at which they occur: Primary infection, Acute HIV Syndrome, Wide dissemination of virus, Seeding of lymphoid organs, Clinical latency, Constitutional Symptoms, Opportunistic disease, Death.
See pg. 165 in First Aid
As CD4 count decreases in HIV-positive adults, what risks increase?
(1) Reactivation of past infections (e.g., TB, HSV, shingles) (2) Dissemination of bacterial and/or fungal infections (e.g., coccidioidomycosis) (3) Non-Hodgkin’s lymphomas
What are common systemic clinical presentations in HIV-positive adults? What is the causative pathogen? What are associated findings/labs?
Low grade fevers, cough, hepatosplenomegaly, tongue ulcer; Histoplasma capsulatum (causes only pulmonary symptoms in immunocompetent hosts); Oval yeast cells within macrophages, CD4 < 100 cells/mm^3
What effect does Histoplasma capsulatum have on HIV-positive adults versus immunocompetent hosts?
HIV-POSITIVE ADULTS - Low grade fevers, cough, splenomegaly, tongue ulcer; IMMUNOCOMPETENT - Only pulmonary symptoms
Again, what effect does Histoplasma capsulatum have on HIV-positive adults? What are its associated findings/labs?
Systemic - Low grade fever, cough, splenomegaly, tongue ulcer; Oval yeast cells within macrophages, CD4 < 100 cells/mm^3
What are 3 common dermatologic clinical presentations in HIV-positive adults? What pathogen causes each?
(1) Fluffy white cottage-cheese lesions - C. albicans (2) Hairy leukoplakia - EBV (3) Superficial vascular proliferation - Bartonella henselae
What pathogen causes fluffly white cottage-cheese lesions in HIV-positive adults? What are the associated findings/labs?
C. albicans (causes thrush and esophagitis); Pseudohyphae, commonly oral if CD4 < 400 cells/mm^3, esophageal if CD4 < 100 cells/mm^3
What pathogen causes Superficial vascular proliferation in HIV-positive adults? What are the associated findings/labs?
Bartonella henselae (causes bacillary angiomatosis); Biopsy reveals neutrophil inflammation
In general, what do C. albicans, EBV, and Bartonella henselae both cause in HIV-positive adults? What disease/condition should you associate with each pathogen?
All cause dermatologic clinical presentation; C. albicans causes oral thrush and esophagitis, EBV causes hairy leukoplakia, and Bartonella henselae causes bacillary angiomatosis
What is a common gastrointestinal clinical presentation in HIV-positive adults? What pathogen causes it? What are the associated findings/labs?
Chronic, watery diarrhea; Cryptosporidium spp.; Acid-fast cysts seen in stool especially when CD4 < 200 cells/mm^3
What are the common neurology clinical presentations in HIV-positive adults? What is the pathogen that causes each?
(1) Encephalopathy - JC virus reactivation (cause of PML) (2) Abscess - Toxoplasma gondii (3) Meningitis - Crytococcus neoformans (4) Retinitis - CMV (5) Dementia - Directly associated with HIV
What pathogen/process causes encephalopathy in HIV-positive adults? What findings/lab may you expect to see in this case?
JC virus reactivation (cause of PML); Due to reactivation of a latent virus, results in demyelination, CD4 < 200 cells/mm^3
What pathogen causes abscesses in HIV-positive adults? What findings/lab may you expect to see in this case?
Toxoplasma gondii; Many ring-enhancing lesions on imaging, CD4 < 100 cells/mm^3
What pathogen causes meningitis in HIV-positive adults? What findings/lab may you expect to see in this case?
Crytococcus neoformans; Indian ink stain reveals yeast with narrow-based budding and large capsule, CD4 < 50 cells/mm^3
What pathogen causes retinitis in HIV-positive adults? What findings/lab may you expect to see in this case?
CMV; Cotton-wool spots on funduscopic exam and may also occur with esophagitis, CD4 < 50 cells/mm^3
What pathogen causes dementia in HIV-positive adults? What is the purpose/relevance of findings/lab in this case?
Directly associated with HIV; Must differentiate from other causes
What are the common oncologic clinical presentations in HIV-positive adults? What is the pathogen that causes each?
(1) Non-Hodgkin’s lymphoma (large cell type) - May be associated with EBV (2) Primary CNS lymphoma - Often associated with eBV (3) Squamous cell carcinoma - HPV (4) Superficial neoplastic proliferation of vasculature - HHV-8 (causes Karposi’s sarcoma, do not confuse with bacillary angiomatosis caused by B. henselae)
What pathogen causes superficial neoplastic proliferation of vasculature in HIV-positive adults? What findings/lab may you expect to see in this case?
HHV-8 (causes Karposi’s carcoma, do NOT confuse with bacillary angiomatosis caused by B. henselae); Biopsy reveals lymphocyte infiltration
What pathogen causes Non-Hodgkin’s lymphoma (large cell type) in HIV-positive adults? What findings/lab may you expect to see in this case?
May be associated with EBV; Often on oropharynx (Waldeyer’s ring)
What pathogen causes Squamous cell carcinoma in HIV-positive adults? What findings/lab may you expect to see in this case?
HPV; Often in anus (men who have sex with men) or cervis (female)
What pathogen causes primary CNS lymphoma in HIV-positive adults? What findings/lab may you expect to see in this case, and what is important to do?
Often associated with EBV; Focal or multiple, differentiate from toxoplasmosis
What are the common respiratory clinical presentations in HIV-positive adults? What is the pathogen that causes each?
(1) Interstitial pneumonia - CMV (2) Invasive aspergillosis - Aspergillus fumigatus (3) Pneumocystis Pneumonia - Pneumocystis jirovecii (4) Pneumonia - S. pneumoniae (5) Tuberculosis-like disease - Mycobacterium avium-intracellulare (aka Mycobacterium avium complex or MAC)
What pathogen causes interstitial pneumonia in HIV-positive adults? What findings/lab may you expect to see in this case?
CMV; Biopsy reveals cells with intranuclear (owl’s eyes) inclusion bodies
What pathogen causes invasive aspergillosis in HIV-positive adults? What findings/lab may you expect to see in this case?
Aspergillus fumigatus; Pleuritic pain, hemoptysis, infiltrates on imaging
What pathogens cause pneumonia in HIV-positive adults? What findings/lab may you expect to see in each case?
(1) Pneumocystis jirovecii; Especially with CD4 < 200 cells/mm^3 (2) S. pneumonia: generally with CD4+ < 200 cells/mm^3
What pathogen causes tuberculosis-like disease in HIV-positive adults? What findings/lab may you expect to see in this case?
Mycobacterium avium-intracellulare (aka Mycobacterium avium complex or MAC); Especially with CD4 < 50 cells/mm^3
What pathogen causes Hairy leukoplakia in HIV-positive adults? What is (are) the associated finding/lab(s)?
EBV; Often on lateral tongue
