Phenotypic characterisation of Human Immunodeficiency Virus type 1 Envelope entry efficiency of transmitted/founder variants circulating in Mbeya, Tanzania

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Zenda Loren Woodman Philippe Selhorst‎ Andile Nofemela Gama Bandawe Michael Hoelscher Leonard Maboko Jinny Marais

Abstract

Background:  Altered fitness of transmitted founder (T/F) HIV-1 variants has been linked to slowed disease progression, yet almost all of these studies have focussed on the role of attenuating immune escape mutations in T/F Gag or entry efficiency of Envelope (Env) in long-term non-progressors (LTNP) and elite suppressors (ES) during chronic stages of infection. As Env could also play an important role in viral fitness during early infection, we investigated if T/F Env entry efficiency, prior to immune selection, affected viral loads of progressors in vivo.  

Findings: Functional Env clones from eight progressors and one LTNP, representing the T/F virus responsible for clinical infection, were constructed. Subsequently Env pseudoviruses (PSVs) were generated, and confirmed to be all R5 but not macrophage tropic. PSVs had a ~80 fold range in entry efficiencies using TZM-bl cells with the LTNP being the poorest enterer. Enhanced entry was associated with increased viral load at 3 months although this association was reduced by 12 months. Finally, we show that entry efficiency was influenced by fusion capacity, CCR5/CD4 dependency, and/or incorporation of gp120 into pseudovirions.

Conclusion:  The variation in TZM-bl entry efficiency of T/F viruses was due to one or more advantageous Env attributes. Viruses with high entry efficiency may have a replication advantage subsequent to transmission, leading to increased viral loads during early infection of progressors.

Article Details

How to Cite
WOODMAN, Zenda Loren et al. Phenotypic characterisation of Human Immunodeficiency Virus type 1 Envelope entry efficiency of transmitted/founder variants circulating in Mbeya, Tanzania. Medical Research Archives, [S.l.], v. 2, n. 2, sep. 2015. ISSN 2375-1924. Available at: <http://www.journals.ke-i.org/index.php/mra/article/view/359>. Date accessed: 20 sep. 2017. doi: https://doi.org/10.18103/mra.v2i2.359.
Keywords
HIV, transmission, entry efficiency, disease progression
Section
Research Articles

References

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