ABSTRACT
Aim To establish and optimize the VSVG/HIV-1NL4-3 Luc pseudovirus model for anti-HIV drugs screening. Methods The infectivity of VSVG/HIV-1 NL4-3 Luc in 4 different cell lines was investigated according to the method of the lucifer-ase activity analysis system of Promega company. 3 different ex-perimental settings were used to detect the activities of approved anti-HIV drugs to confirm the feasibility and effectiveness of the system. Finally, some potential compounds were screened for their anti-HIV activities, and their antiviral activities against the pseudovirus were compared with HIV-1ⅢB . Results The pseud-ovirus showed the strongest replication ability in CRFK cells, and a clear dose-effect relationship was found between the report gene expression level and the virus quantity. Comparing the EC50 of different positive inhibitors against VSVG/HIV-1 NL4-3 Luc on 3 kinds of experimental conditions, 3rd scheme is the best. Finally, the system was used to screen compounds, the EC50 s a-gainst pseudovirus were similar to those in HIV-1ⅢB . Conclusion An optimized VSVG/HIV-1 NL4-3 Luc anti-HIV screening sys-tem has been successfully developed.
ABSTRACT
The pseudotype virus is a virus nucleic acids packaged by another virus envelope protein, to form the virus with the exogenous virus envelope and maintain virus genome characteristics of itself. Due to the loss of its ability to self-replicate and high safety, pseudoviruses are widely used as safe substitutes for infectious virus in virology studies, such as HIV, H5N1 and HCV Here we will introduce the advantages and limitations of pseudoviruses, and through summarizing a large number of research achievements, we prove pseudoviruses are feasible and effective as an antiviral drug screening platform. The platform is safe and reliable and it will make more contribution in antiviral drug research.
ABSTRACT
It was recently shown that several new synthetic 2-alkylsulfanyl-6-benzyl-3, 4-dihydropyrimidin-4(3H)-one (S-DABO) derivatives demonstrated anti-HIV-1 activity. Three of the derivatives namely RZK-4, RZK-5 and RZK-6 were used in this study to explore their inhibitory effects on a variety of HIV strains. These compounds at a concentration of 200 microg mL(-1) almost completely inhibited the activity of recombinant HIV-1 reverse transcriptase. All of the three compounds reduced replication of HIV-1 laboratory-derived strains, low-passage clinical isolated strain, and the drug resistant strain. In particular RZK-6 showed potent activity against the HIV-1 drug resistant strain. In general, the antiviral activities are similar in magnitude to nevirapine (NVP), which is a non-nucleoside reverse transcriptase inhibitor approved by FDA. The therapeutic indexes of these compounds were remarkable, ranging from 3704 to 38462 indicating extremely low cytotoxicity. These results suggest that the three S-DABO derivatives in this study have good potential for further development in anti-HIV-1 therapy. It may be particularly useful to target at the non-nucleoside reverse transcriptase inhibitors resistant HIV-1 strain.
ABSTRACT
In the present research, two Chinese rhesus monkeys were inoculated intravenously with 5000 TCID50 of SIVmac239. The changes in the numbers of CD4+T lymphocyte in peripheral blood,plasma viral loads, proviral DNA and humoral antibodies against virus were periodically monitored during 121 days. At the early stage of infection, proviral DNA had been detected in PBMCs, and infectious SIVmac239 virus had been isolated from PBMCs. At the same period, the numbers of CD4+T lymphocytes were significantly decreased, and maintained at low level during the 121-day period of infection. Plasma viral loads reached the peak at week 2 post-inoculation and kept at a steady state subsequently. Moreover, antibodies against viral proteins were detected from plasma. All the results showed that the two Chinese rhesus monkeys had been infected with SIVmac239 successfully. This animal model can be applied for further AIDS researches.
ABSTRACT
Protein kinase C (PKC) belongs to the family of phospholipid-dependent serine/threonine kinase. PKC signaling has been implicated in the development of multiple human diseases including the central nervous system dysfunctions and cardiovascular disorders. It has been demonstrated that PKC can stimulate viral activation through multiple mechanisms and phosphorylate the HIV-1 p17 gag,Nef,Vif and Rev proteins as well. The phosphorylation of these proteins may have significant effects on HIV replication. Members of the PKC family participate at many levels in diverse signal transduction pathways involved in HIV cycles. PKC inhibition may be considered a logical mechanism which inhibits HIV-1 replication. Agents that induce HIV-1 replication could be used in conjunction with HAART to decrease or eliminate the latent reservoirs by forcing viral expression. A better understanding of the role of PKC could in form the search of specific target for new anti-HIV therapies.