•Adult T-cell Leukemia (ATL):large numbers of lymphocytes,skin lesions, lymphadenopathy,hepatosplenomegaly; relativelyindolent•Tropical Spastic Paraperesis(TSP): demyelinationof longmotor neurons, stiff gait withspasticity and hyperreflexia,Infects most non-dividing cells,but does not transform. Chronicpersistent infection due toability to escape immunecontrolHuman RetrovirusesHIVViralCharacteristics•Enveloped•Negative polarity ssRNAgenome•Diploid•Retrovirus: ssRNAreverse transcribed to generate dsDNA, followed byintegration into the host genome as pro-virusPathogenesis•Targets: CD4+ T lymphocytes (GALT, lymph nodes, spleen, thymus),macrophages, dendriticcells, brain macrophages and microglia•Different anatomical sites often harbor distinct, but phylogeneticallyrelated HIV-1 genotypes due to tissue-specific target cell characteristics, immunologicalpressures, and antiretroviral penetrationNatural History•Virus expands with a doubling time of 12 hours; about 1011particles generateddaily•Acute infection (14-21 days post exposure): 1-100 million viral particles; may beasymptomatic or have meningitis, fever, rash•T cell response reduces viral load, resulting in a chronic infective steady statelevel that depends on host HLA haplotype(production = clearance)•Over time, CD4 cell count is gradually depleted due to cytolyticviral production,increasing susceptibility to opportunistic infections . Plasma viral RNA reflects therate of CD4 cell decline.ClinicalManifestations•HIV –associated neurological disorders (HAND) in 50% of untreated patients•GALT has memory T-cells (because constantly exposed to antigen) that expressCCR5, the co-receptor that makes it universally infectable. As a result, all of theGALT is depleted in acute infection•As CD4 cell counts decline, more infections with pathogens that are inherentlyspasticity and hyperreflexia,lower extremity weakness,urinary incontinence, sensoryneuropathyTransmission•Vertical,via breast milk•Blood•Sex•Sex•Blood•PerinatalTreatment•ATL: cytotoxicchemotherapywith steroids•TSP: corticoor androgenicsteroids•NOT ART•ARTRetrovirus Genesgag: internal structuralgenespol: genes for protease,reverse transcriptaseenv: envelope genes(accessory genes inlentiviruses)2 terminal repeats•As CD4 cell counts decline, more infections with pathogens that are inherentlyless virulentHost Response•Some antibodies directed against HIV envelope can neutralize virions; but therapid changes in HIV make vaccine development difficult•CytotoxicT lymphocytes and specific HLA haplotypescan determine whetherprogression is rapid or slow; heterozygoteshave a better prognosis thanhomozygotes•CD4+ Helper cells are important, but these are destroyed by HIV with timeHIV Accessory GenesVifInhibits host cell apobec3G/3F(which deaminatescytosinesin the viral DNA, leading to Gbarb2rightA hypermutationanddegradation) by inducing proteasomaldegradation of apobec3G/3F.
