Human immunodeficiency virus

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Presentation transcript:

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

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

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

COINFECTION CONSECUTIVE INFECTION HETEROZYGOTE VIRUS RECOMBINANT VIRUS

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)

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

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

HIV, SIV Chimpanzee (Pan troglodytes)

Sooty Mangabey

HIV seropositive individuals in Hungary

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

Sequence diversity, Hungarian isolates, C2V3 region (env) 17.5±3.4% (8.6-24.6)

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

HIV-1 surface glycoprotein (gp120)

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

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)