HIV-1 is characterized by high genetic heterogeneity which is a challenge for developing therapeutics. Therefore, it is necessary to understand the extent of genetic variations that HIV is undergoing in North India. The objective of this study was to determine the role of genetic and functional role of Vif on APOBEC3G degradation. Vif is an accessory protein involved in counteracting APOBEC3/F proteins. Genetic analysis of Vif variants revealed that Vif C variants were closely related to South African Vif C whereas Vif B variants and Vif B/C showed distinct geographic locations. This is the first report to show the emergence of Vif B/C in our population. The functional domains, motifs and phosphorylation sites were well conserved. Vif C variants differed in APOBEC3G degradation from Vif B variants. Vif B/C revealed similar levels of APOBEC3G degradation to Vif C confirming the presence of genetic determinants in C-terminal region. High genetic diversity was observed in Vif variants which may cause the emergence of more complex and divergent strains. These results reveal the genetic determinants of Vif in mediating APOBEC3G degradation and highlight the genetic information for the development of anti-viral drugs against HIV. Importance: Vif is an accessory HIV-1 protein which plays significant role in the degradation of human DNA-editing factor APOBEC3G, thereby impeding the antiretroviral activity of APOBEC3G. It is known that certain natural polymorphisms in Vif could degrade APOBEC3G relatively higher rate, suggesting its role in HIV-1 pathogenesis. This is the first report from North India showcasing genetic variations and novel polymorphisms in Vif gene. Subtype C is prevalent in India, but for the first time we observed putative B/C recombinants with a little high ability to degrade APOBEC3G indicating adaptation and evolving nature of virus in our population. Indian Vif C variants were able to degrade APOBEC3G well in comparison to Vif B variants. These genetic changes were most likely selected during adaptation of HIV to our population. These results elucidate that the genetic determinants of Vif and highlights the potential targets for therapeutics.
This data represents the effect of miR-155 on the expression of commonly used housekeeping genes, GAPDH, Beta Actin, RPL13A, and U6. The human miR-155 and control RNA were transfected to A549 cells by electroporation. Expression of these genes was compared in both groups by real-time PCR. The significant up-regulation in the expression of GAPDH was observed in the miR-155 transfected samples as compared to control while no major change was observed in the expression of the other three genes.
The deployment of viruses as vaccine-vectors has witnessed recent developments owing to a better understanding of viral genomes and mechanism of interaction with the immune system. Vaccine delivery by viral vectors offers various advantages over traditional approaches. Viral vector vaccines are one of the best candidates for activating the cellular arm of the immune system, coupled with the induction of significant humoral responses. Hence, there is a broad scope for the development of effective vaccines against many diseases using viruses as vectors. Further studies are required before an ideal vaccine-vector is developed and licensed for use in humans. In this article, we have outlined the use of retroviral vectors in developing vaccines against various viral diseases.
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