Hybrid spreading mechanisms and T cell activation shape the dynamics of HIV-1 infection
- PMID: 25837979
- PMCID: PMC4383537
- DOI: 10.1371/journal.pcbi.1004179
Hybrid spreading mechanisms and T cell activation shape the dynamics of HIV-1 infection
Abstract
HIV-1 can disseminate between susceptible cells by two mechanisms: cell-free infection following fluid-phase diffusion of virions and by highly-efficient direct cell-to-cell transmission at immune cell contacts. The contribution of this hybrid spreading mechanism, which is also a characteristic of some important computer worm outbreaks, to HIV-1 progression in vivo remains unknown. Here we present a new mathematical model that explicitly incorporates the ability of HIV-1 to use hybrid spreading mechanisms and evaluate the consequences for HIV-1 pathogenenesis. The model captures the major phases of the HIV-1 infection course of a cohort of treatment naive patients and also accurately predicts the results of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) trial. Using this model we find that hybrid spreading is critical to seed and establish infection, and that cell-to-cell spread and increased CD4+ T cell activation are important for HIV-1 progression. Notably, the model predicts that cell-to-cell spread becomes increasingly effective as infection progresses and thus may present a considerable treatment barrier. Deriving predictions of various treatments' influence on HIV-1 progression highlights the importance of earlier intervention and suggests that treatments effectively targeting cell-to-cell HIV-1 spread can delay progression to AIDS. This study suggests that hybrid spreading is a fundamental feature of HIV infection, and provides the mathematical framework incorporating this feature with which to evaluate future therapeutic strategies.
Conflict of interest statement
The authors have declared that no competing interests exist.
Figures
![Fig 1](http://178.128.105.246/cars-https-www.ncbi.nlm.nih.gov/pmc/articles/instance/4383537/bin/pcbi.1004179.g001.gif)
![Fig 2](http://178.128.105.246/cars-https-www.ncbi.nlm.nih.gov/pmc/articles/instance/4383537/bin/pcbi.1004179.g002.gif)
![Fig 3](http://178.128.105.246/cars-https-www.ncbi.nlm.nih.gov/pmc/articles/instance/4383537/bin/pcbi.1004179.g003.gif)
![Fig 4](http://178.128.105.246/cars-https-www.ncbi.nlm.nih.gov/pmc/articles/instance/4383537/bin/pcbi.1004179.g004.gif)
![Fig 5](http://178.128.105.246/cars-https-www.ncbi.nlm.nih.gov/pmc/articles/instance/4383537/bin/pcbi.1004179.g005.gif)
![Fig 6](http://178.128.105.246/cars-https-www.ncbi.nlm.nih.gov/pmc/articles/instance/4383537/bin/pcbi.1004179.g006.gif)
Similar articles
-
Immune signatures for HIV-1 and HIV-2 induced CD4+T cell dysregulation in an Indian cohort.BMC Infect Dis. 2019 Feb 11;19(1):135. doi: 10.1186/s12879-019-3743-7. BMC Infect Dis. 2019. PMID: 30744575 Free PMC article.
-
A hybrid stochastic-deterministic computational model accurately describes spatial dynamics and virus diffusion in HIV-1 growth competition assay.J Theor Biol. 2012 Nov 7;312:120-32. doi: 10.1016/j.jtbi.2012.07.005. Epub 2012 Jul 17. J Theor Biol. 2012. PMID: 22814476
-
Anti-Tat immunity defines CD4+ T-cell dynamics in people living with HIV on long-term cART.EBioMedicine. 2021 Apr;66:103306. doi: 10.1016/j.ebiom.2021.103306. Epub 2021 Apr 7. EBioMedicine. 2021. PMID: 33839064 Free PMC article.
-
Innate immune recognition of HIV-1.Immunity. 2012 Sep 21;37(3):389-98. doi: 10.1016/j.immuni.2012.08.011. Immunity. 2012. PMID: 22999945 Free PMC article. Review.
-
T-cell exhaustion in HIV infection.Immunol Rev. 2019 Nov;292(1):149-163. doi: 10.1111/imr.12823. Immunol Rev. 2019. PMID: 31883174 Free PMC article. Review.
Cited by
-
Functionalized gold nanoparticles: promising and efficient diagnostic and therapeutic tools for HIV/AIDS.RSC Med Chem. 2020 Oct 1;11(11):1252-1266. doi: 10.1039/d0md00298d. eCollection 2020 Nov 18. RSC Med Chem. 2020. PMID: 34095839 Free PMC article. Review.
-
Estimating the basic reproduction number of a pathogen in a single host when only a single founder successfully infects.PLoS One. 2020 Jan 10;15(1):e0227127. doi: 10.1371/journal.pone.0227127. eCollection 2020. PLoS One. 2020. PMID: 31923263 Free PMC article.
-
A threshold delay model of HIV infection of newborn infants through breastfeeding.Infect Dis Model. 2019 May 16;4:188-214. doi: 10.1016/j.idm.2019.05.001. eCollection 2019. Infect Dis Model. 2019. PMID: 31194190 Free PMC article.
-
Experimental and computational analyses reveal that environmental restrictions shape HIV-1 spread in 3D cultures.Nat Commun. 2019 May 13;10(1):2144. doi: 10.1038/s41467-019-09879-3. Nat Commun. 2019. PMID: 31086185 Free PMC article.
-
Accounting for Space—Quantification of Cell-To-Cell Transmission Kinetics Using Virus Dynamics Models.Viruses. 2018 Apr 17;10(4):200. doi: 10.3390/v10040200. Viruses. 2018. PMID: 29673154 Free PMC article.
References
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials