Imperial College London
Alternate

ProfessorJillGilmour

Faculty of Medicine, Department of Infectious Disease

Honorary Principal Research Fellow 
 
 
 
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Contact

 

+44 (0)20 3315 5098j.gilmour

 
 
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Location

 

J.2.3 Immunology DepartmentChelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Macharia:2020:10.1371/journal.ppat.1008853,
author = {Macharia, GN and Yue, L and Staller, E and Dilernia, D and Wilkins, D and Song, H and McGowan, E and King, D and Fast, P and Imami, N and Price, MA and Sanders, EJ and Hunter, E and Gilmour, J},
doi = {10.1371/journal.ppat.1008853},
journal = {PLoS Pathogens},
pages = {1--22},
title = {Infection with multiple HIV-1 founder variants is associated with lower viral replicative capacity, faster CD4(+)T cell decline and increased immune activation during acute infection},
url = {http://dx.doi.org/10.1371/journal.ppat.1008853},
volume = {16},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - HIV-1 transmission is associated with a severe bottleneck in which a limited number of variants from a pool of genetically diverse quasispecies establishes infection. The IAVI protocol C cohort of discordant couples, female sex workers, other heterosexuals and men who have sex with men (MSM) present varying risks of HIV infection, diverse HIV-1 subtypes and represent a unique opportunity to characterize transmitted/founder viruses (TF) where disease outcome is known. To identify the TF, the HIV-1 repertoire of 38 MSM participants’ samples was sequenced close to transmission (median 21 days post infection, IQR 18–41) and assessment of multivariant infection done. Patient derived gag genes were cloned into an NL4.3 provirus to generate chimeric viruses which were characterized for replicative capacity (RC). Finally, an evaluation of how the TF virus predicted disease progression and modified the immune response at both acute and chronic HIV-1 infection was done. There was higher prevalence of multivariant infection compared with previously described heterosexual cohorts. A link was identified between multivariant infection and replicative capacity conferred by gag, whereby TF gag tended to be of lower replicative capacity in multivariant infection (p = 0.02) suggesting an overall lowering of fitness requirements during infection with multiple variants. Notwithstanding, multivariant infection was associated with rapid CD4+ T cell decline and perturbances in the CD4+ T cell and B cell compartments compared to single variant infection, which were reversible upon control of viremia. Strategies aimed at identifying and mitigating multivariant infection could contribute toward improving HIV-1 prognosis and this may involve strategies that tighten the stringency of the transmission bottleneck such as treatment of STI. Furthermore, the sequences and chimeric viruses help with TF based experimental vaccine immunogen design and can be used in functional assays to pr
AU  - Macharia,GN
AU  - Yue,L
AU  - Staller,E
AU  - Dilernia,D
AU  - Wilkins,D
AU  - Song,H
AU  - McGowan,E
AU  - King,D
AU  - Fast,P
AU  - Imami,N
AU  - Price,MA
AU  - Sanders,EJ
AU  - Hunter,E
AU  - Gilmour,J
DO  - 10.1371/journal.ppat.1008853
EP  - 22
PY  - 2020///
SN  - 1553-7366
SP  - 1
TI  - Infection with multiple HIV-1 founder variants is associated with lower viral replicative capacity, faster CD4(+)T cell decline and increased immune activation during acute infection
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1008853
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000570246900002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008853
UR  - http://hdl.handle.net/10044/1/83228
VL  - 16
ER  -
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