Dataset Information

Multi-scale immunoepidemiological modeling of within-host and between-host HIV dynamics: systematic review of mathematical models.

ABSTRACT:

Objective

The objective of this study is to conduct a systematic review of multi-scale HIV immunoepidemiological models to improve our understanding of the synergistic impact between the HIV viral-immune dynamics at the individual level and HIV transmission dynamics at the population level.

Background

While within-host and between-host models of HIV dynamics have been well studied at a single scale, connecting the immunological and epidemiological scales through multi-scale models is an emerging method to infer the synergistic dynamics of HIV at the individual and population levels.

Methods

We reviewed nine articles using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework that focused on the synergistic dynamics of HIV immunoepidemiological models at the individual and population levels.

Results

HIV immunoepidemiological models simulate viral immune dynamics at the within-host scale and the epidemiological transmission dynamics at the between-host scale. They account for longitudinal changes in the immune viral dynamics of HIV+ individuals, and their corresponding impact on the transmission dynamics in the population. They are useful to analyze the dynamics of HIV super-infection, co-infection, drug resistance, evolution, and treatment in HIV+ individuals, and their impact on the epidemic pathways in the population. We illustrate the coupling mechanisms of the within-host and between-host scales, their mathematical implementation, and the clinical and public health problems that are appropriate for analysis using HIV immunoepidemiological models.

Conclusion

HIV immunoepidemiological models connect the within-host immune dynamics at the individual level and the epidemiological transmission dynamics at the population level. While multi-scale models add complexity over a single-scale model, they account for the time varying immune viral response of HIV+ individuals, and the corresponding impact on the time-varying risk of transmission of HIV+ individuals to other susceptibles in the population.

SUBMITTER: Dorratoltaj N

PROVIDER: S-EPMC5623312 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multi-scale immunoepidemiological modeling of within-host and between-host HIV dynamics: systematic review of mathematical models.

Dorratoltaj Nargesalsadat N Nikin-Beers Ryan R Ciupe Stanca M SM Eubank Stephen G SG Abbas Kaja M KM

PeerJ 20170928

<h4>Objective</h4>The objective of this study is to conduct a systematic review of multi-scale HIV immunoepidemiological models to improve our understanding of the synergistic impact between the HIV viral-immune dynamics at the individual level and HIV transmission dynamics at the population level.<h4>Background</h4>While within-host and between-host models of HIV dynamics have been well studied at a single scale, connecting the immunological and epidemiological scales through multi-scale models ...[more]

PMID: 28970973

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Project description:Human immunodeficiency virus-1 (HIV-1) employs accessory proteins to evade innate immune responses by neutralizing the anti-viral activity of host restriction factors. Apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, A3G) and bone marrow stromal cell antigen 2 (BST2) are host resistance factors that potentially inhibit HIV-1 infection. BST2 reduces viral production by tethering budding HIV-1 particles to virus producing cells, while A3G inhibits the reverse transcription (RT) process and induces viral genome hypermutation through cytidine deamination, generating fewer replication competent progeny virus. Two HIV-1 proteins counter these cellular restriction factors: Vpu, which reduces surface BST2, and Vif, which degrades cellular A3G. The contest between these host and viral proteins influences whether HIV-1 infection is established and progresses towards AIDS. In this work, we present an age-structured multi-scale viral dynamics model of in vivo HIV-1 infection. We integrated the intracellular dynamics of anti-viral activity of the host factors and their neutralization by HIV-1 accessory proteins into the virus/cell population dynamics model. We calculate the basic reproductive ratio (Ro) as a function of host-viral protein interaction coefficients, and numerically simulated the multi-scale model to understand HIV-1 dynamics following host factor-induced perturbations. We found that reducing the influence of Vpu triggers a drop in Ro, revealing the impact of BST2 on viral infection control. Reducing Vif?s effect reveals the restrictive efficacy of A3G in blocking RT and in inducing lethal hypermutations, however, neither of these factors alone is sufficient to fully restrict HIV-1 infection. Interestingly, our model further predicts that BST2 and A3G function synergistically, and delineates their relative contribution in limiting HIV-1 infection and disease progression. We provide a robust modeling framework for devising novel combination therapies that target HIV-1 accessory proteins and boost antiviral activity of host factors.

Dataset Information

Multi-scale immunoepidemiological modeling of within-host and between-host HIV dynamics: systematic review of mathematical models.

Objective

Background

Methods

Results

Conclusion

Publications

Multi-scale immunoepidemiological modeling of within-host and between-host HIV dynamics: systematic review of mathematical models.

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