Figure 7
Figure 7. Kinetics of differential gene expression corresponds with the 2 phases of HIV-1 processing by dendritic cells (DCs). (A) Routes of entry of HIV-1 into DCs. Following initial binding of HIV-1 to C-type lectin receptors (CLRs) on the cell surface, HIV-1 can enter the DC by 1 of 2 routes. (1) More than 95% of the virus is rapidly endocytosed resulting in processing by the endolysosomal pathway and degradation by acid proteolysis in late endosomes. (2) The remaining less than 5% of attached virus is transferred to cell surface CD4/CCR5 resulting in fusion of the viral envelope with the DC plasma membrane and entry of the capsid into cytoplasm, resulting in reverse transcription, HIV-1 cDNA generation (first detected < 24 hours after infection = second phase of de novo replication), and then the later stages of viral replication and assembly. (B) Corresponding HIV-1 nucleic acid levels in DCs after HIV-1 treatment. The graph shows a representation of the HIV-1 nucleic acid levels after treatment of DCs. As shown by the dotted line, at time 0 the high levels of HIV-1 nucleic acid represents input virions. The nucleic acid levels then rapidly decrease to undetectable levels by 20 hours after infection as the vast majority of HIV-1 enters and is destroyed by late endosomes. As shown by the solid line, 20 hours after infection viral nucleic acid levels begin to slowly rise, representing progeny virions resulting from productive infection by the small amount of virus that was able to fuse with the plasma membrane and initiate a productive infection. (C) Temporal differential gene expression corresponds to the kinetics of the 2 phases of HIV-1 processing by DCs. At 6 hours, a burst of gene expression was seen as a consequence of viral entry into the DC (predominantly via endocytosis). By 24 hours, most of the virus that entered via endocytosis has been degraded and virions that entered by fusion with the plasma membrane have yet to undergo replication. Correspondingly very few genes are differentially expressed at this time point. At 48 hours, a fresh burst of gene expression is detected, representing genes differentially expressed as a result of HIV-1 replication in DCs.

Kinetics of differential gene expression corresponds with the 2 phases of HIV-1 processing by dendritic cells (DCs). (A) Routes of entry of HIV-1 into DCs. Following initial binding of HIV-1 to C-type lectin receptors (CLRs) on the cell surface, HIV-1 can enter the DC by 1 of 2 routes. (1) More than 95% of the virus is rapidly endocytosed resulting in processing by the endolysosomal pathway and degradation by acid proteolysis in late endosomes. (2) The remaining less than 5% of attached virus is transferred to cell surface CD4/CCR5 resulting in fusion of the viral envelope with the DC plasma membrane and entry of the capsid into cytoplasm, resulting in reverse transcription, HIV-1 cDNA generation (first detected < 24 hours after infection = second phase of de novo replication), and then the later stages of viral replication and assembly. (B) Corresponding HIV-1 nucleic acid levels in DCs after HIV-1 treatment. The graph shows a representation of the HIV-1 nucleic acid levels after treatment of DCs. As shown by the dotted line, at time 0 the high levels of HIV-1 nucleic acid represents input virions. The nucleic acid levels then rapidly decrease to undetectable levels by 20 hours after infection as the vast majority of HIV-1 enters and is destroyed by late endosomes. As shown by the solid line, 20 hours after infection viral nucleic acid levels begin to slowly rise, representing progeny virions resulting from productive infection by the small amount of virus that was able to fuse with the plasma membrane and initiate a productive infection. (C) Temporal differential gene expression corresponds to the kinetics of the 2 phases of HIV-1 processing by DCs. At 6 hours, a burst of gene expression was seen as a consequence of viral entry into the DC (predominantly via endocytosis). By 24 hours, most of the virus that entered via endocytosis has been degraded and virions that entered by fusion with the plasma membrane have yet to undergo replication. Correspondingly very few genes are differentially expressed at this time point. At 48 hours, a fresh burst of gene expression is detected, representing genes differentially expressed as a result of HIV-1 replication in DCs.

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