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The life cycle of HIV

来源:本站整理  发布时间:2010/11/24 10:03:13

The life cycle of HIV. HIV-1 infection begins with virus binding to a susceptible target cell via a specific interaction between the viral gp120 envelope glycoprotein and the CD4 cell-surface receptor (step 1). After binding, a process of membrane fusion, facilitated by the viral gp41 envelope glycoprotein and by the CXCR4 and CCR5 proteins, results in the introduction of the HIV-1 particle into the cell cytoplasm (step 2). In activated and proliferating T lymphocytes, reverse transcription of the viral RNA (step 3) and the integration of resulting DNA copy into the host-cell chromosome ensues (step 4). In resting cells, however, these events proceed inefficiently. Once integrated into the chromosome, the transcription activity of the HIV-1 provirus is regulated by constitutive host-cell transcription factors (step 5). Transcription initially results in the early synthesis of regulatory HIV-1 proteins, such as tat or rev. Tat binds to the TAR (transactivation response element) site at the beginning of the HIV-1 RNA in the nucleus and stimulates transcription and formation of longer RNA transcripts. After synthesis of a full-length viral RNA, an array of spliced viral messenger RNAs (mRNAs) can be produced. The differential expression of distinct species of viral mRNAs is controlled by the HIV-1 rev protein. The level of rev present in an infected cell determines the preferential production of the unspliced or singly spliced RNAs or the multiply spliced mRNAs that encode the viral regulatory gene products (step 6). Once a sufficient level of rev accumulates, the singly spliced and unspliced HIV-1 RNAs appear in the cytoplasm, and the synthesis of viral structural proteins can proceed (step 7). HIV-1 particles assemble at the host-cell surface (step 8) and acquire viral env proteins as they bud through the host-cell membrane. The viral gag and pol polyproteins are cleaved by viral protease during or shortly after budding, generating mature infectious virions (step 9).

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