2,379 research outputs found
An in-host model of HIV incorporating latent infection and viral mutation
We construct a seven-component model of the in-host dynamics of the Human
Immunodeficiency Virus Type-1 (i.e, HIV) that accounts for latent infection and
the propensity of viral mutation. A dynamical analysis is conducted and a
theorem is presented which characterizes the long time behavior of the model.
Finally, we study the effects of an antiretroviral drug and treatment
implications.Comment: 10 pages, 7 figures, Proceedings of AIMS Conference on Differential
Equations and Dynamical Systems (2015
Opportunistic infection as a cause of transient viremia in chronically infected HIV patients under treatment with HAART
When highly active antiretroviral therapy is administered for long periods of
time to HIV-1 infected patients, most patients achieve viral loads that are
``undetectable'' by standard assay (i.e., HIV-1 RNA copies/ml). Yet
despite exhibiting sustained viral loads below the level of detection, a number
of these patients experience unexplained episodes of transient viremia or viral
"blips". We propose here that transient activation of the immune system by
opportunistic infection may explain these episodes of viremia. Indeed, immune
activation by opportunistic infection may spur HIV replication, replenish viral
reservoirs and contribute to accelerated disease progression. In order to
investigate the effects of concurrent infection on chronically infected HIV
patients under treatment with highly active antiretroviral therapy (HAART), we
extend a simple dynamic model of the effects of vaccination on HIV infection
[Jones and Perelson, JAIDS 31:369-377, 2002] to include growing pathogens. We
then propose a more realistic model for immune cell expansion in the presence
of pathogen, and include this in a set of competing models that allow low
baseline viral loads in the presence of drug treatment. Programmed expansion of
immune cells upon exposure to antigen is a feature not previously included in
HIV models, and one that is especially important to consider when simulating an
immune response to opportunistic infection. Using these models we show that
viral blips with realistic duration and amplitude can be generated by
concurrent infections in HAART treated patients.Comment: 30 pages, 9 figures, 1 table. Submitted to Bulletin of Mathematical
Biolog
Inferring HIV escape rates from multi-locus genotype data
Cytotoxic T-lymphocytes (CTLs) recognize viral protein fragments displayed by
major histocompatibility complex (MHC) molecules on the surface of virally
infected cells and generate an anti-viral response that can kill the infected
cells. Virus variants whose protein fragments are not efficiently presented on
infected cells or whose fragments are presented but not recognized by CTLs
therefore have a competitive advantage and spread rapidly through the
population. We present a method that allows a more robust estimation of these
escape rates from serially sampled sequence data. The proposed method accounts
for competition between multiple escapes by explicitly modeling the
accumulation of escape mutations and the stochastic effects of rare multiple
mutants. Applying our method to serially sampled HIV sequence data, we estimate
rates of HIV escape that are substantially larger than those previously
reported. The method can be extended to complex escapes that require
compensatory mutations. We expect our method to be applicable in other contexts
such as cancer evolution where time series data is also available
Regulation of T cell expansion by antigen presentation dynamics
An essential feature of the adaptive immune system is the proliferation of
antigen-specific lymphocytes during an immune reaction to form a large pool of
effector cells. This proliferation must be regulated to ensure an effective
response to infection while avoiding immunopathology. Recent experiments in
mice have demonstrated that the expansion of a specific clone of T cells in
response to cognate antigen obeys a striking inverse power law with respect to
the initial number of T cells. Here, we show that such a relationship arises
naturally from a model in which T cell expansion is limited by decaying levels
of presented antigen. The same model also accounts for the observed dependence
of T cell expansion on affinity for antigen and on the kinetics of antigen
administration. Extending the model to address expansion of multiple T cell
clones competing for antigen, we find that higher affinity clones can suppress
the proliferation of lower affinity clones, thereby promoting the specificity
of the response. Employing the model to derive optimal vaccination protocols,
we find that exponentially increasing antigen doses can achieve a nearly
optimized response. We thus conclude that the dynamics of presented antigen is
a key regulator of both the size and specificity of the adaptive immune
response
A Simple Cellular Automaton Model for Influenza A Viral Infections
Viral kinetics have been extensively studied in the past through the use of
spatially homogeneous ordinary differential equations describing the time
evolution of the diseased state. However, spatial characteristics such as
localized populations of dead cells might adversely affect the spread of
infection, similar to the manner in which a counter-fire can stop a forest fire
from spreading. In order to investigate the influence of spatial
heterogeneities on viral spread, a simple 2-D cellular automaton (CA) model of
a viral infection has been developed. In this initial phase of the
investigation, the CA model is validated against clinical immunological data
for uncomplicated influenza A infections. Our results will be shown and
discussed.Comment: LaTeX, 12 pages, 18 EPS figures, uses document class ReTeX4, and
packages amsmath and SIunit
Correlations in the T Cell Response to Altered Peptide Ligands
The vertebrate immune system is a wonder of modern evolution. Occasionally,
however, correlations within the immune system lead to inappropriate
recruitment of preexisting T cells against novel viral diseases. We present a
random energy theory for the correlations in the naive and memory T cell immune
responses. The non-linear susceptibility of the random energy model to
structural changes captures the correlations in the immune response to mutated
antigens. We show how the sequence-level diversity of the T cell repertoire
drives the dynamics of the immune response against mutated viral antigens.Comment: 21 pages; 6 figures; to appear in Physica
Kinetics of acute hepatitis B virus infection in humans
Using patient data from a unique single source outbreak of hepatitis B virus (HBV) infection, we have characterized the kinetics of acute HBV infection by monitoring viral turnover in the serum during the late incubation and clinical phases of the disease in humans. HBV replicates rapidly with minimally estimated doubling times ranging between 2.2 and 5.8 d (mean 3.7 ± 1.5 d). After a peak viral load in serum of nearly 1010 HBV DNA copies/ml is attained, clearance of HBV DNA follows a two or three phase decay pattern with an initial rapid decline characterized by mean half-life (t1/2) of 3.7 ± 1.2 d, similar to the t1/2 observed in the noncytolytic clearance of covalently closed circular DNA for other hepadnaviruses. The final phase of virion clearance occurs at a variable rate (t1/2 of 4.8 to 284 d) and may relate to the rate of loss of infected hepatocytes. Free virus has a mean t1/2 of at most 1.2 ± 0.6 d. We estimate a peak HBV production rate of at least 1013 virions/day and a maximum production rate of an infected hepatocyte of 200–1,000 virions/day, on average. At this peak rate of virion production we estimate that every possible single and most double mutations would be created each day
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