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Human immunodeficiency virus
Janos Minarovits, M.D., D.Sc. Microbiological Research Group, National Center for Epidemiology Budapest
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Retroviridae (family) -coding for reverse transcriptase RNA→DNA
Oncornavirinae (subfamily): HTLV I & II Lentivirinae (subfamily): HIV-1, HIV-2 Spumavirinae (subfamily): human foamy virus
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Retroviridae, basic observations
Transduction of cellular oncogenes Promoter insertion Non-cytopathic viruses (Oncornavirinae, Spumavirinae) Viral interference
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COINFECTION CONSECUTIVE INFECTION HETEROZYGOTE VIRUS RECOMBINANT VIRUS
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Lentivirinae, clinical features
Symptomps appear after a long period of incubation Immunosuppression Involvement of the haemopoietic system Involvement of the central nervous system Autoimmunity may develop (arthritis)
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Lentivirinae Species-specific, exogenous, non-oncogenic viruses
▪ Cytopathic effect in certain host cells but not in macrophages ▪ Accumulation of non-integrated cDNA in infected cells ▪ Latent infection of certain host cells
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Lentivirinae, molecular virological features
Relatively large genome (9 kb) Several processed gag proteins, heavily glycosylated env proteins Genetic variability, especially in env A new open regaing frame between pol and env Coding of „accessory” proteins
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HIV, SIV Chimpanzee (Pan troglodytes)
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Sooty Mangabey
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HIV seropositive individuals in Hungary
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Phylogenetic analysis
gp120 Nested PCR PCR1 PCR2 Nested PCR PCR1 PCR2 Cloning (TOPO TA klónozó kit) Heteroduplex mobility assay HMA Sequencing Phylogenetic analysis PHYLIP
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Sequence diversity, Hungarian isolates, C2V3 region (env)
17.5±3.4% ( )
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HIV, major routes of transmission
Sexual contact HIV infected blood or tissue Mother to child ● Homosexual ● I.v. drug users, shared needles ● Transplacental ●Heterosexual ●Blood transfusion ● During birth ● Artificial insemination ● Blood products ● Milk ● Organ or bone marrow transplantation ● Contaminated medical devices
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HIV-1 surface glycoprotein (gp120)
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Amino acid sequences of Hungarian HIV-1 isolates from treated patients, C2V3 region, env
V3 régió tetramer szekvenciái GPGR GPGK GPGS GRGR GHRR GPGQ Előfordulási gyakoriság 5 2 1
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NSI (non-syncytium-inducing)
HIV-1, biological phenotypes NSI Vírus SI Vírus SI Vírus NSI (non-syncytium-inducing) SI (syncytium-inducing) asymptomatic stage macrophage tropic growth: slow/low CCR5 usage (R5 vírus) symptomatic stage T-cell tropic growth: rapid/high CXCR4 usage (X4 vírus)
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