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Viral Replication: Positive and Negative Host Co-Factors
Wednesday, 1:30 - 3:30 pm
Background: APOBEC3G, also known as CEM15, is a broad antiretroviral host factor by deaminating dC to dU in the minus strand DNA of HIV-1, other lentiviruses, and murine leukemia virus, thereby creating G to A hypermutation in the plus strand DNA to inhibit the infectivity of these viruses. In this study, we examined the antiretroviral function of murine homologue of APOBEC3G on several retrovirus systems using different producer cells to elucidate more detail mechanisms how APOBEC3G regulates the virion infectivity of a wide variety of retroviruses.
Methods: Luciferase reporter HIV-1 viruses with or without vif were prepared in HEK293T cells with or without expression of human or murine APOBEC3G. Productive infection of these viruses was determined by the luciferase assay. Luciferase reporter murine retroviruses were prepared in human or murine producer cells with or without expression of human or murine APOBEC3G. Productive infection of murine retroviruses was determined by the luciferase assay. Hypermutation in HIV-1 or murine retroviral DNA was sequenced using DNA from endogenous reverse transcription or provirus DNA integrated into target cells.
Results: Murine APOBEC3G did not suppress the infectivity of murine retroviral vectors produced from human cells or murine cells, whereas it showed the antiviral activity on both wild type and delta-vif virions of HIV-1 in human cells. Human APOBEC3G showed a broad antiviral activity on HIV-1 and murine retroviral vectors produced from human cells as well as murine cells. 3) Functional interaction study between human and murine APOBEC3G or between HIV-1 and murine retrovirus showed that murine APOBEC3G did not function on murine retrovirus.
Conclusions: Murine APOBEC3G did not show the antiretroviral activity on murine retroviruses and had different target specificity from that of human APOBEC3G. Human APOBEC3G worked as an antiviral factor not only in human cells but also in murine cells. These results suggest that murine retrovirus could replicate in murine target cells expressing murine APOBEC3G because it is not a target for this enzyme.
Keywords: APOBEC3G; HIV-1; murine retrovirus