alexa Abstract | Nef Deletion in HIV-1eli Eliminates Peripheral CD4 T-Cell Loss in a Humanized BLT Mouse Model of HIV Disease

International Journal of Drug Development and Research
Open Access

OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations

700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Research Article Open Access

Abstract

Background: Humans infected with HIV-1 containing nef gene deletions show very slow or non-progression to AIDS. Therefore, a nef-deleted HIV-1 may be useful in generating a pathogenically-attenuated candidate therapeutic HIV-1 vaccine. We have created a mutant of HIV-1eli lacking a functional nef gene. In this study we have characterized the pathogenic phenotype of this mutant in an animal model of HIV-1 disease.

Methods and findings: We determined the contribution of the nef gene to replication and infectivity in cell culture and to pathogenesis in humanized BLT mice after infection with HIV-1eli, a CXCR4-tropic subtype D virus. We constructed a nef-null virus to create HIV-1eliΔnef. Human peripheral blood mononuclear cell cultures from 13 different donors were infected and viral growth was monitored for 14 days. HIV-1eli produced higher p24 levels compared to HIV-1eliΔnef, indicating lower viral replication. HIV-1eli and HIV-1eliΔnef were then used to infect humanized BLT mice. Viremia was delayed several weeks in the HIV-1eliΔnef-infected mice compared to HIV-1eli. Viremia was evident in the majority of mice infected with HIV-1eli by 3 weeks post-infection while viremia was not evident in any HIV-1eliΔnef infected mice until 7 weeks post-infection. Mice infected with HIV-1eli harbored an average of 2.94e5 ± 1.6e5 copies of viral RNA/ml in blood. In contrast, blood from mice infected with HIV-1eliΔnef harbored an average of 4.4e3 ± 4.5e3 copies of viral RNA/ml; a ~1.5-log reduction in average viremia. Flow cytometry revealed that all mice infected with HIV-1eli showed a precipitous decline in the ratio of human CD4+ to CD8+ T-cells in peripheral blood from week 1 to week 7 post-infection. In sharp contrast, none of the mice infected with HIV-1eliΔnef showed a sustained decline of CD4+ to CD8+ T-cells from week 1 to week 10 post-infection.

Conclusions: We conclude that nef is necessary for high levels of viral replication both in vitro and in vivo and for depletion of peripheral CD4+ T-cells in HIV-1eli, a pathological hallmark of HIV-1 disease. We have generated and characterized a pathogenically-attenuated mutant of HIV-1eli lacking a functional nef gene in a humanized mouse model of HIV-1 disease.

To read the full article Peer-reviewed Article PDF image | Peer-reviewed Full Article image

Author(s): Clever JL Tam SM Rold CJ Strings VR Wadekar S Lira V Fatehi E Bansal N Martin V and Apte S

Keywords

HIV/AIDS pathogenesis, HIV-replication, Animal models of HIV disease, Drug development and Drug research

 
Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords