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Human immunodeficiency virus

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1 Human immunodeficiency virus
Janos Minarovits, M.D., D.Sc. Microbiological Research Group, National Center for Epidemiology Budapest

2 Retroviridae (family) -coding for reverse transcriptase RNA→DNA
Oncornavirinae (subfamily): HTLV I & II Lentivirinae (subfamily): HIV-1, HIV-2 Spumavirinae (subfamily): human foamy virus

3 Retroviridae, basic observations
Transduction of cellular oncogenes Promoter insertion Non-cytopathic viruses (Oncornavirinae, Spumavirinae) Viral interference

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19 COINFECTION CONSECUTIVE INFECTION HETEROZYGOTE VIRUS RECOMBINANT VIRUS

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21 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)

22 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

23 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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25 HIV, SIV Chimpanzee (Pan troglodytes)

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27 Sooty Mangabey

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30 HIV seropositive individuals in Hungary

31 Phylogenetic analysis
gp120 Nested PCR PCR1 PCR2 Nested PCR PCR1 PCR2 Cloning (TOPO TA klónozó kit) Heteroduplex mobility assay HMA Sequencing Phylogenetic analysis PHYLIP

32 Sequence diversity, Hungarian isolates, C2V3 region (env)
17.5±3.4% ( )

33 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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38 HIV-1 surface glycoprotein (gp120)

39 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

40 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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