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


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.

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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: <>. Date accessed: 20 sep. 2017. doi:
HIV, transmission, entry efficiency, disease progression
Research Articles


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