scholarly journals Accounting for multi-delay effects in an HIV-1 infection model with saturated infection rate, recovery and proliferation of host cells

BIOMATH ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 2012297
Author(s):  
Debadatta Adak ◽  
Nandadulal Bairagi ◽  
Robert Hakl
Keyword(s):  
Infection Rate ◽  
Viral Entry ◽  
Host Cells ◽  
Infection Model ◽  
Multiple Delays ◽  
Delay Effects ◽  
Delayed System ◽  
Infected Cells ◽  
Disease Free ◽  
Hiv 1

Biological models inherently contain delay. Mathematical analysis of a delay-induced model is, however, more difficult compare to its non-delayed counterpart. Difficulties multiply if the model contains multiple delays. In this paper, we analyze a realistic HIV-1 infection model in the presence and absence of multiple delays. We consider self-proliferation of CD4+T cells, nonlinear saturated infection rate and recovery of infected cells due to incomplete reverse transcription in a basic HIV-1 in-host model and incorporate multiple delays to account for successful viral entry and subsequent virus reproduction from the infected cell. Both of delayed and non-delayed system becomes disease-free if the basic reproduction number is less than unity. In the absence of delays, the infected equilibrium is shown to be locally asymptotically stable under some parametric space and unstable otherwise. The system may show unstable oscillatory behaviour in the presence of either delay even when the non-delayed system is stable. The second delay further enhances the instability of the endemic equilibrium which is otherwise stable in the presence of a single delay. Numerical results are shown to be in agreement with the analytical results and reflect quite realistic dynamics observed in HIV-1 infected individuals.

scholarly journals A Fractional Order Model for Viral Infection with Cure of Infected Cells and Humoral Immunity

2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Adnane Boukhouima ◽  
Khalid Hattaf ◽  
Noura Yousfi
Keyword(s):  
Viral Infection ◽  
Humoral Immunity ◽  
Host Cells ◽  
Infection Model ◽  
Order Model ◽  
Fractional Order Model ◽  
Infected Cells ◽  
Fractional Differential ◽  
Well Posed ◽  
Viral Infection Model

In this paper, we study the dynamics of a viral infection model formulated by five fractional differential equations (FDEs) to describe the interactions between host cells, virus, and humoral immunity presented by antibodies. The infection transmission process is modeled by Hattaf-Yousfi functional response which covers several forms of incidence rate existing in the literature. We first show that the model is mathematically and biologically well-posed. By constructing suitable Lyapunov functionals, the global stability of equilibria is established and characterized by two threshold parameters. Finally, some numerical simulations are presented to illustrate our theoretical analysis.

scholarly journals Determination of Number of Infected Cells and Concentration of Viral Particles in Plasma during HIV-1 Infections Using Shehu Transformation

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
M. Higazy ◽  
Sudhanshu Aggarwal ◽  
Y. S. Hamed
Keyword(s):  
Initial Conditions ◽  
Integral Transformation ◽  
Mathematical Representation ◽  
Infection Model ◽  
Viral Particles ◽  
Infected Cells ◽  
Linear Differential ◽  
The Mathematical Model ◽  
Ordinary Linear Differential Equations ◽  
Hiv 1

In this paper, the authors determine the number of infected cells and concentration of infected (viral) particles in plasma during HIV-1 (human immunodeficiency virus type one) infections using Shehu transformation. For this, the authors first defined some useful properties of Shehu transformation with proof and then applied Shehu transformation on the mathematical representation of the HIV-1 infection model. The mathematical model of HIV-1 infections contains a system of two simultaneous ordinary linear differential equations with initial conditions. Results depict that Shehu transformation is very effective integral transformation for determining the number of infected cells and concentration of viral particles in plasma during HIV-1 infections.

scholarly journals Differential Ability of Primary HIV-1 Nef Isolates To Downregulate HIV-1 Entry Receptors

2015 ◽  
Vol 89 (18) ◽  
pp. 9639-9652 ◽  
Author(s):  
Mako Toyoda ◽  
Yoko Ogata ◽  
Macdonald Mahiti ◽  
Yosuke Maeda ◽  
Xiaomei T. Kuang ◽  
...  
Keyword(s):  
Viral Replication ◽  
Viral Entry ◽  
Immune Escape ◽  
Elite Controllers ◽  
Functional Impairments ◽  
Disease Phenotypes ◽  
Infected Cells ◽  
Entry Receptor ◽  
Hiv 1

ABSTRACTHIV-1 Nef downregulates the viral entry receptor CD4 as well as the coreceptors CCR5 and CXCR4 from the surface of HIV-infected cells, and this leads to promotion of viral replication through superinfection resistance and other mechanisms. Nef sequence motifs that modulate these functions have been identified viain vitromutagenesis with laboratory HIV-1 strains. However, it remains unclear whether the same motifs contribute to Nef activity in patient-derived sequences and whether these motifs may differ in Nef sequences isolated at different infection stages and/or from patients with different disease phenotypes. Here,nefclones from 45 elite controllers (EC), 46 chronic progressors (CP), and 43 acute progressors (AP) were examined for their CD4, CCR5, and CXCR4 downregulation functions. Nef clones from EC exhibited statistically significantly impaired CD4 and CCR5 downregulation ability and modestly impaired CXCR4 downregulation activity compared to those from CP and AP. Nef's ability to downregulate CD4 and CCR5 correlated positively in all cohorts, suggesting that they are functionally linkedin vivo. Moreover, impairments in Nef's receptor downregulation functions increased the susceptibility of Nef-expressing cells to HIV-1 infection. Mutagenesis studies on three functionally impaired EC Nef clones revealed that multiple residues, including those at novel sites, were involved in the alteration of Nef functions and steady-state protein levels. Specifically, polymorphisms at highly conserved tryptophan residues (e.g., Trp-57 and Trp-183) and immune escape-associated sites were responsible for reduced Nef functions in these clones. Our results suggest that the functional modulation of primary Nef sequences is mediated by complex polymorphism networks.IMPORTANCEHIV-1 Nef, a key factor for viral pathogenesis, downregulates functionally important molecules from the surface of infected cells, including the viral entry receptor CD4 and coreceptors CCR5 and CXCR4. This activity enhances viral replication by protecting infected cells from cytotoxicity associated with superinfection and may also serve as an immune evasion strategy. However, how these activities are maintained under selective pressurein vivoremains elusive. We addressed this question by analyzing functions of primary Nef clones isolated from patients at various infection stages and with different disease phenotypes, including elite controllers, who spontaneously control HIV-1 viremia to undetectable levels. The results indicated that downregulation of HIV-1 entry receptors, particularly CCR5, is impaired in Nef clones from elite controllers. These functional impairments were driven by rare Nef polymorphisms and adaptations associated with cellular immune responses, underscoring the complex molecular pathways responsible for maintaining and attenuating viral protein functionin vivo.

GLOBAL DYNAMICS OF A DELAYED HIV-1 INFECTION MODEL WITH ABSORPTION AND SATURATION INFECTION

2012 ◽  
Vol 05 (03) ◽  
pp. 1260012 ◽  
Author(s):  
RUI XU
Keyword(s):  
Viral Entry ◽  
Chronic Infection ◽  
Infection Model ◽  
Global Dynamics ◽  
Asymptotically Stable ◽  
Basic Reproduction Ratio ◽  
Globally Asymptotically Stable ◽  
Reproduction Ratio ◽  
Virus Particles ◽  
Hiv 1

In this paper, an HIV-1 infection model with absorption, saturation infection and an intracellular delay accounting for the time between viral entry into a target cell and the production of new virus particles is investigated. By analyzing the characteristic equations, the local stability of an infection-free equilibrium and a chronic-infection equilibrium of the model is established. By using suitable Lyapunov functionals and LaSalle's invariance principle, it is proved that if the basic reproduction ratio is less than unity, the infection-free equilibrium is globally asymptotically stable; and if the basic reproduction ratio is greater than unity, sufficient condition is derived for the global stability of the chronic-infection equilibrium.

scholarly journals Structural Basis of CD4 Downregulation by HIV-1 Nef

2020 ◽  
Author(s):  
Yonghwa Kwon ◽  
Robyn Kaake ◽  
Ignacia Echeverria ◽  
Marissa Suarez ◽  
Charlotte Stoneham ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Immune Surveillance ◽  
Underlying Mechanism ◽  
Host Cells ◽  
Structural Basis ◽  
Viral Glycoprotein ◽  
Class I Mhc ◽  
Hiv 1

The HIV-1 protein Nef suppresses multiple immune surveillance mechanisms to promote viral pathogenesis1. Individuals infected with HIV-1 encoding defective nef genes do not develop AIDS for decades2,3. A key target of Nef is the cellular receptor CD4. Although essential for viral entry into host cells, CD4 is problematic for the virus later in its replication cycle: CD4 disrupts processing of the viral glycoprotein, Env, inhibiting infectivity4; it interferes with the release of new virions5,6; and it causes vulnerability to superinfection, causing premature cell death and limiting viral productivity7. Furthermore, binding of CD4 to Env exposes otherwise-concealed Env epitopes, rendering infected cells more susceptible to antibody-dependent cellular cytotoxicity and virus particles more susceptible to neutralizing antibodies8-10. HIV-1 has evolved strategies to mitigate these problems. Newly synthesized CD4 is targeted in the endoplasmic reticulum by the viral Vpu protein for proteasomal degradation11. Surface-expressed CD4, in contrast, is targeted by Nef for endocytosis and lysosomal degradation12-15. Nef’s effect on CD4 involves hijacking of clathrin adaptor complex 2 (AP2)-dependent endocytosis16,17. Although how Nef associates with a part of the tetrameric AP2 is understood18, a complete understanding of the interaction, especially how CD4 is sequestered by Nef into a complex with AP2, has remained elusive. Here, we present a high-resolution crystal structure that describes the underlying mechanism. An intricate combination of conformational changes occurs in both Nef and AP2 to enable CD4 binding and downregulation. Strikingly, a pocket on Nef previously identified as crucial for recruiting class I MHC is also responsible for recruiting CD4, revealing a potential approach to inhibit two of Nef’s activities and sensitize the virus to immune clearance

scholarly journals Cryo-ET of HIV reveals Env positioning on Gag lattice and structural variation among Env trimers

2021 ◽  
Author(s):  
Vidya Mangala Prasad ◽  
Daniel P. Leaman ◽  
Klaus N. Lovendahl ◽  
Mark A. Benhaim ◽  
Edgar A. Hodge ◽  
...  
Keyword(s):  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Structural Variation ◽  
Electron Tomography ◽  
Host Cells ◽  
Detailed Characterization ◽  
Cryo Electron Tomography ◽  
Structural Mass Spectrometry ◽  
Structural Mass ◽  
Hiv 1

SummaryHIV-1 Env mediates viral entry into host cells and is the sole target for neutralizing antibodies. However, Env structure and organization in its native virion context has eluded detailed characterization. Here we used cryo-electron tomography to analyze Env in mature and immature HIV-1 particles. Immature particles showed distinct Env positioning relative to the underlying Gag lattice, providing insights into long-standing questions about Env incorporation. A 9.1Å sub-tomogram averaged reconstruction of virion-bound Env in conjunction with structural mass spectrometry revealed unexpected features, including a variable central core of the gp41 subunit, heterogeneous glycosylation between protomers plus a flexible stalk that allows Env tilting and variable exposure of neutralizing epitopes. Together, our results provide an integrative understanding of HIV assembly and structural variation in Env antigen presentation.

scholarly journals HTLV-1 contains a high CG dinucleotide content and is susceptible to the host antiviral protein ZAP

Retrovirology ◽  
2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Paola Miyazato ◽  
Misaki Matsuo ◽  
Benjy J. Y. Tan ◽  
Michiyo Tokunaga ◽  
Hiroo Katsuya ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Production ◽  
Host Cells ◽  
Cell Leukaemia ◽  
Leukaemia Virus ◽  
Delta Type ◽  
Infected Cells ◽  
Cg Dinucleotide ◽  
Hiv 1

Abstract Background Human T cell leukaemia virus type 1 (HTLV-1) is a retrovirus associated with human diseases such as adult T-cell leukaemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis. In contrast to another human retrovirus, human immunodeficiency virus type 1 (HIV-1), HTLV-1 persists in the host not via vigorous virus production but mainly via proliferation and/or long-term survival in the form of silent proviruses in infected host cells. As a result, HTLV-1-infected cells rarely produce virus particles in vivo even without anti-retroviral treatment. That should be an advantage for the virus to escape from the host immune surveillance by minimizing the expression of viral antigens in host cells. However, why HIV-1 and HTLV-1 behave so differently during natural infection is not fully understood. Results We performed cap analysis of gene expression (CAGE) using total RNAs and nascent, chromatin-associated, RNAs in the nucleus and found that HTLV-1 RNAs were processed post-transcriptionally in infected cells. RNA processing was evident for the sense viral transcripts but not the anti-sense ones. We also found a higher proportion of CG di-nucleotides in proviral sequences of HTLV-1-infected cells, when compared to the HIV-1 genomic sequence. It has been reported recently that CG dinucleotide content of viral sequence is associated with susceptibility to the antiviral ZC3HAV1 (ZAP), suggesting the involvement of this protein in the regulation of HTLV-1 transcripts. To analyse the effect of ZAP on HTLV-1 transcripts, we over-expressed it in HTLV-1-infected cells. We found there was a dose-dependent reduction in virus production with ZAP expression. We further knocked down endogenous ZAP with two independent targeting siRNAs and observed a significant increase in virus production in the culture supernatant. Other delta-type retroviruses such as simian T-cell leukaemia virus and bovine leukaemia virus, also contain high CG-dinucleotide contents in their viral genomes, suggesting that ZAP-mediated suppression of viral transcripts might be a common feature of delta-type retroviruses, which cause minimal viremia in their natural hosts. Conclusions The post-transcriptional regulatory mechanism involving ZAP might allow HTLV-1 to maintain a delicate balance required for prolonged survival in infected individuals.

scholarly journals Global Stability of an HIV-1 Infection Model with General Incidence Rate and Distributed Delays

2014 ◽  
Vol 2014 ◽  
pp. 1-10
Author(s):  
Abdoul Samba Ndongo ◽  
Hamad Talibi Alaoui
Keyword(s):  
Incidence Rate ◽  
Viral Entry ◽  
Disease Transmission ◽  
Transmission Function ◽  
Infection Model ◽  
Global Dynamics ◽  
General Incidence Rate ◽  
Delay Differential ◽  
Hiv 1 ◽  
Intracellular Delays

In this work an HIV-1 infection model with nonlinear incidence rate and distributed intracellular delays and with humoral immunity is investigated. The disease transmission function is assumed to be governed by general incidence rate f(T,V)V. The intracellular delays describe the time between viral entry into a target cell and the production of new virus particles and the time between infection of a cell and the emission of viral particle. Lyapunov functionals are constructed and LaSalle invariant principle for delay differential equation is used to establish the global asymptotic stability of the infection-free equilibrium, infected equilibrium without B cells response, and infected equilibrium with B cells response. The results obtained show that the global dynamics of the system depend on both the properties of the general incidence function and the value of certain threshold parameters R0 and R1 which depends on the delays.

Coxsackievirus B transmission and possible new roles for extracellular vesicles

2013 ◽  
Vol 41 (1) ◽  
pp. 299-302 ◽  
Author(s):  
Jameel M. Inal ◽  
Samireh Jorfi
Keyword(s):  
Calcium Concentration ◽  
Rna Virus ◽  
Extracellular Vesicle ◽  
Host Cells ◽  
Physical Interaction ◽  
Enveloped Viruses ◽  
Coxsackievirus B ◽  
Infected Cells ◽  
Adenovirus Receptor ◽  
Hiv 1

Coxsackievirus B1, a member of the Picornaviridae family is a non-enveloped single-stranded RNA virus associated with human diseases including myocarditis and pancreatitis. Infection of the intestinal mucosa, lined by polarized epithelial cells, requires interaction of coxsackievirus with apically located DAF (decay-accelerating factor) before transport to the basolaterally located CAR (coxsackie and adenovirus receptor), where entry is mediated by endocytosis. As with many other non-enveloped viruses, coxsackievirus has to induce lysis of host cells in order to perpetuate infection. However, recent evidence indicates that virus spread to secondary sites is not only achieved by a lytic mechanism and a non-lytic cell–cell strategy has been suggested for coxsackievirus B3. A physical interaction between infected and non-infected cells has been shown to be an efficient mechanism for retroviral transmission and one type of extracellular vesicle, the exosome, has been implicated in HIV-1 transmission. HIV-1 also takes advantage of depolymerization of actin for spread between T-cells. Calpain-mediated depolymerization of the actin cytoskeleton, as a result of increases in intracellular calcium concentration during coxsackievirus infection, would result in a release of host cell-derived microvesicles. If so, we speculate that maybe such microvesicles, increasingly recognized as major vehicles mediating intercellular communication, could play a role in the intercellular transmission of non-enveloped viruses.

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