HIV Flashcards
Classification of Retroviruses
Simple retroviruses encode
gag, pol, and env genes
Complex viruses also encode
accessory genes (HIV: tat, rev, nef, vif, vpu)
slow viruses assoc. with neurologic and immunosuppressive disease
Lentiviruses
Gag
group-specific antigen (core and capsid proteins)
Pol
polymerase (reverse transcriptase, protease and integrase)
Env
envelope (glycoproteins)
HIV characteristics
RNA Viruses, ss, (+) sense, RT
HIV pic
4 accessory genes HIV
(vif, vpr, vpu, nef)
2 regulatory genes (virus-host interactions) HIV
tat
rev
Binding and Fusion HIV characteristics
begins by binding to a CD4 receptor and co-receptor on the surface of a CD4+ T-lymphocyte fuses with the host cell releases RNA into host cell
Integration HIV
Newly formed HIV DNA enters the host cell’s nucleus
→ HIV integrase helps insert the HIV DNA within the host cell’s own DNA
integrated HIV DNA: provirus
→ The provirus may remain inactive for several years, producing few / no new copies of HIV
Transcription HIV
Host cell receives a signal to become active provirus uses a host RNA polymerase to copy the HIV genomic material and mRNA
Assembly HIV
HIV protease “cuts” the long chains of HIV proteins into smaller individual proteins (smaller HIV proteins assemble with copies of HIV genome new virus particle)
Budding HIV
Newly assembled virus buds from the host cell
- takes part of the cell’s outer envelope (is studded with HIV glycoproteins)
- HIV glycoproteins: necessary for virus to bind CD4 and co-receptors, allowing them to move on to infect other cells
Which HIV subtype is found in the US
HIV-B
HIV replication cycle
- Fusion
- Entry
- Viral DNA via RT
- Viral DNA: transport to nucleus, integration 5. New vRNA genomic RNA, viral proteins
- New vRNA + proteins move to cell surface new, immature, HIV virus
- Virus matures by protease releasing individual HIV proteins
HIV – Transmission
• Infected individual’s blood, semen or vaginal fluid
– Unprotected anal, vaginal, oral sex w/ infected individuals
– Share needles / syringes w/ infected individuals
- Increased risk with other STI infections
- HIV does not survive for long periods of time outside host
characteristics of newly infected HIV pts
About 97% are in low and middle income countries
About 1000 are in children under 15 years of age
About 6000 are in adults aged 15 years and older, of whom:
─ almost 48% are among women
─ about 42% are among young people (15-24)
HIV – Pathogenesis
virus tropism for CD4- expressing T cells and macrophage lineage cells
– multipotent hematopoietic stem and progenitor cells
Dendritic cells
– Accumulate the virus particles on their surfaces, but do not usually internalize them
– carry virus to lymph nodes resulting in efficient infection of CD4+ T cells
Mechanisms of immune evasion HIV
– antigenic variation
– carbohydrate masking of target epitopes
– conformational changes
by viral envelope to mask neutralization targets
– downregulation of host HLA
– viral latency in resting T cells and antigen- presenting cells
HIV encephalopathy CPEs
Cells appear to be the result of syncytial fusion of HIV-infected macrophages and microglia
Virus spread cell to cell; immune circulatory antibodies cannot have an effect
Syncytia often seen in the brain
HIV - Diagnosis methods
Antibody or antigen testing (usually within a few weeks of infection), ELISA / Western Blot
After CDC reccomendations, how much of a reduction in AIDS was seen over years
95% rate drop
Mortality and highly active antiretroviral therapy (HAART) use
Significant drops in HIV deaths
Percentage of people eligible who are receiving antiretroviral therapy highest in what nations
Latin america
Course of HIV Progression
Typical/rapid/ nonprogression
- Typical progression – 80%, 7-10 yrs
- Rapid progression – 5-10%, within 2 yrs
- Non-progression
– 10-15%, no disease ~7-10+ yrs
– CD4 count stays high, viral load not detectable (no medications)
Course of HIV Progression graph
• Window period
– Negative HIV test (primary infection to sero- conversion)
– Viral load very high, high transmission risk
• Acute retroviral syndrome
– Symptoms can have a huge range – WIDE DIFFERENTIAL DIAGNOSIS
• Opportunistic infections
– GOAL is to prevent these from occurring – Greatly increase chance of death
Acquired Immunodeficiency Syndrome (AIDS)
• final stage of HIV infection
– virus has weakened the immune system to the point at which the body has a difficult time fighting infection
Progression of AIDS
1) acute infection
2) strong anti-HIV immune defense
3) a latent reservoir
4) loss of CD4+ cells and loss of immune response
5) onset of AIDS
Bacterial pneumonia in AIDS cause
Common cause is Streptococcus pneumoniae
Streptococcus pneumoniae, Virulence
colonize oropharynx (surface protein adhesions),
spread into normally sterile tissues
(pneumolysin, IgA protease), stimulate
local inflammatory response (teichoic acid, peptidoglycan fragments, pneumolysin), and evade phagocytic killing (polysaccharide capsule)
Mycobacterium avium complex (MAC) in AIDS
CD4 count?
species?
CD4 <50
M. avium and M. intracellulare
Mycobacterium avium complex characteristics
Weakly Gram +, strongly acid-fast aerobic rods
• Disease: host response to infection
– asymptomatic colonization, chronic localized pulmonary disease, solitary nodule
– disseminated disease (particularly in patients w/ AIDS)
• Tissues can be filled w/ Mycobacteria; 100s – 1000s
bacteria / ml of blood
Mycobacterium avium complex infection types/progess
(1) pulmonary MAC: immunocompetent hosts
(2) disseminated MAC: individuals w/ advanced AIDS
(3) MAC lymphadenitis in children
leading cause of death among people living with AIDS
Tuberculosis (TB)
– common opportunistic infection associated w/ HIV
infection pretty common in HIV + people
Salmonellosis
Bartonella henselae characteristics
(Gram – rod)
– Bacillary angiomatosis: vascular proliferative
disease in immunocompromised patients
– Infection primarily involves skin, lymph nodes, or liver and spleen
– Subacute endocarditis
– Cat-scratch disease: chronic regional lymphadenopathy assoc. w/ cat scratch
Bacillary angiomatosis
appears as purplish to bright red skin patches, often resembling Kaposi’s sarcoma
Bacillary angiomatosis:
reactive vascular proliferation
secondary to infection by
Bartonella henselae
HIV infection + hepatitis, -> more likely to develop
liver toxicity from medications
most common viral
cause of congenital defects
CMV
CMV Establishes latent infection in
mononuclear lymphocytes, stromal cells of bone marrow
CMV member of
Member of Betaherpesvirinae,
CMV damages
Weakened immune system: virus can cause damage to eyes through infection and inflammation
- retina (CMV retinitis, untreated leads to blindness)
- digestive tract
- lungs or other organs
Human Herpesvirus (HHV-1 and -2) in AIDS patients
– HIV increases the probability that infection is more severe, sores may take longer to heal, systemic symptoms may also be more severe (may cause brain damage and blindness)
– Immunocompromised people and neonates are at risk for disseminated, life-threatening disease
Human Papillomavirus (HPV) in AIDS
– Infection w/ both HPV and HIV increases a woman’s risk even further: cervical cancer occurs more often, more aggressively in women who are HIV-positive
Progressive multifocal leukoencephalopathy (PML)/ JC virus
Serious brain infection caused by the human polyomavirus JC virus
- speech problems
- weakness on one side of the body • loss of vision in one eye
- numbness in one arm or leg
– PML usually occurs only when the immune system has been severely damaged
Progressive multifocal leukoencephalopathy
grossly as irregular areas of granularity in white matter, which bear some resemblance to the plaques of
demyelination with multiple sclerosis
Kaposi’s sarcoma, HHV-8 (KSHV) characteristics
– Tumor of the blood vessel walls
– Rare in people not infected with HIV
– Usually appears as pink, red or purple lesions on the skin and mouth (with darker skin, the lesions may look dark brown or black)
THE MOST FREQUENTLY DETECTED TUMORS IN AIDS PATIENTS
Kaposi’s sarcoma, HHV-8 (KSHV)
Non-Hodgkin’s lymphoma: most common w/
inherited immune
deficiency, autoimmune disease, or HIV
Viral infections: HTLV-1, Hep C, and EBV, ↑ risk of
developing
non-Hodgkin’s lymphoma
Fungi that leads to pneumonia in aids patients
Candidiasis
common central nervous system infection
associated with HIV
Cryptococcal meningitis
– caused by a fungus that is present in soil or associated with bird or bat droppings
– does not seem to spread person to person
Cryptococcal meningitis
Cryptococcal meningitis CD4 count
CD4 cell counts are below 100
Major virulence factors Cryptococcus neoformans
polysaccharide capsule, phenol oxidase enzyme, ability to grow at 37°C
Pneumocystis jirovecii (formerly P. carinii, PCP)
– Previously considered to be a protozoan parasite
– Infection almost exclusively in debilitated and immunosupressed patients
Toxoplasmosis
parasite spread primarily by cats
- humans can contract by touching their mouths with their hands after changing cat litter
- eating raw or undercooked meat, especially pork, lamb and venison
– Leads to encephalitis in many patients with AIDS
Cryptosporidiosis
– Infection → intestinal parasite commonly found in animals (ingestion of contaminated food, water)
– Leads to severe, chronic diarrhea in people w/ AIDS
self-limited syndrome in HIV-infected individuals w/ CD4 counts > 200, disease refractory to therapy in individuals w/ suppressed CD4 counts
