Search

Retroviral integration is an essential stage in the life cycle of retroviruses. Viruses need to insert their DNA into the chromosomal DNA of the host cells. Retroviral integration is a complex process which involves viral and host proteins and requires the movement of the retroviral DNA from the cytoplasm to the nucleus. The viral integrase is a key enzyme in this process that catalyzes two reactions: 3´ processing of viral DNA that take place in the cytoplasm following reverse transcription and the strand transfer that inserts viral DNA in a host cell chromosome. Development of a successful treatment for the human immunodeficiency virus (HIV) infection using the strand transfer inhibitor, Raltegravir, has demonstrated that retroviral integration is a suitable step for drug intervention. Different types of inhibitors targeting HIV integrase or any of the other components of the retroviral integration process are currently being designed or developed. This work contains a summary of the retroviral integration process as well as, many of the latest advances in this topic which were exposed at the recently held IVth International Meeting on Retroviral Integration.

A combination of antiviral drugs known as antiretroviral therapy (ART) has shown effectiveness against the human immunodeficiency virus (HIV). ART has markedly decreased mortality and morbidity among HIV-infected patients, having even reduced HIV transmission. However, an important current disadvantage, resistance development, remains to be solved. Hope is focused on developing drugs against cellular targets. This strategy is expected to prevent the emergence of viral resistance. In this study, using a comparative proteomic approach in MT4 cells treated with an anti-HIV leukocyte extract, we identified vimentin, a molecule forming intermediate filaments in the cell, as a possible target against HIV infection. We demonstrated a strong reduction of an HIV-1 based lentivirus expressing the enhanced green fluorescent protein (eGFP) in vimentin knockdown cells, and a noteworthy decrease of HIV-1 capsid protein antigen (CAp24) in those cells using a multiround infectivity assay. Electron micrographs showed changes in the structure of intermediate filaments when MT4 cells were treated with an anti-HIV leukocyte extract. Changes in the structure of intermediate filaments were also observed in vimentin knockdown MT4 cells. A synthetic peptide derived from a cytoskeleton protein showed potent inhibitory activity on HIV-1 infection, and low cytotoxicity. Our data suggest that vimentin can be a suitable target to inhibit HIV-1.

This report summarizes the main topics delivered as lectures at the meeting Frontiers in HIV pathogenesis, Therapy and Eradication, held at the Whistler Conference Centre, in Whistler British Columbia, Canada, in March 26-31. The meeting was organized as part of the Keystone Symposia on Molecular and Cell Biology joined with the conference Cell Biology of Virus Entry. The current status on research for eradicating HIV-1 latent reservoirs and ways to reactivate them for destruction with current or novel antiretroviral therapies were the key topics. Targeted inhibition of virus entry, new classes of inhibitors, animal models for testing antiretroviral therapies and virus cell-to-cell contact-mediated transmission, together with structural analysis of HIV-1 proteins and replication processes, were also presented. The useful discussions at both the oral and poster sessions paved the way for understanding processes essential for future therapeutic attempts to effectively inhibit virus replication and transmission, including its eradication.

Combined anti-retroviral therapy has been really efficient in suppressing HIV replication, but it does not cure the infection. This is due to the permanency of integrated viral DNA in the infected cells. To achieve the HIV cure, the interaction between virus and its host needs to be extremely understood. Because of this, scientific community persists in dedicating efforts to profoundly comprehend the pathogenesis of this virus. The present work summaries important aspects discussed in the last meeting HIV-Pathogenesis, Virus vs. Host. It was held in Fairmont Banff Springs, Banff, Alberta, Canada, March 9-14. The conference debated the latest advances in the biology of HIV-1. Topics as virus entry into the cell, into the host, virus exit, virushost genetics and co-evolution, host-virus interactions and responses, reservoirs, latency, reactivation, HIV and central nervous system, animal models and HIV and the microbiome at the mucosa were updated and deeply discussed. In parallel HIV vaccines: Adaptive Immunity and Beyond meeting was celebrated. The event, part of the Keystone Symposia Global Health Series, was a singular opportunity to analyze the state of HIV research and the new challenges in the battle against HIV infection.