Adaptive Epidemic Dynamics in Networks: Thresholds and Control

Theoretical modeling of computer virus/worm epidemic dynamics is an important problem that has attracted many studies. However, most existing models are adapted from biological epidemic ones. Although biological epidemic models can certainly be adapted to capture some computer virus spreading scenarios (especially when the so-called homogeneity assumption holds), the problem of computer virus spreading is not well understood because it has many important perspectives that are not necessarily accommodated in the biological epidemic models. In this paper we initiate the study of such a perspective, namely that of adaptive defense against epidemic spreading in arbitrary networks. More specifically, we investigate a non-homogeneous Susceptible-Infectious-Susceptible (SIS) model where the model parameters may vary with respect to time. In particular, we focus on two scenarios we call semi-adaptive defense and fully-adaptive} defense, which accommodate implicit and explicit dependency relationships between the model parameters, respectively. In the semi-adaptive defense scenario, the model's input parameters are given; the defense is semi-adaptive because the adjustment is implicitly dependent upon the outcome of virus spreading. For this scenario, we present a set of sufficient conditions (some are more general or succinct than others) under which the virus spreading will die out; such sufficient conditions are also known as epidemic thresholds in the literature. In the fully-adaptive defense scenario, some input parameters are not known (i.e., the aforementioned sufficient conditions are not applicable) but the defender can observe the outcome of virus spreading. For this scenario, we present adaptive control strategies under which the virus spreading will die out or will be contained to a desired level.Comment: 20 pages, 8 figures. This paper was submitted in March 2009, revised in August 2009, and accepted in December 2009. However, the paper was not officially published until 2014 due to non-technical reason

Hybrid spreading mechanisms and T cell activation shape the dynamics of HIV-1 infection

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

The formin FHOD1 and the small GTPase Rac1 promote vaccinia virus actin-based motility

Vaccinia virus dissemination relies on the N-WASP– ARP2/3 pathway, which mediates actin tail formation underneath cell-associated extracellular viruses (CEVs). Here, we uncover a previously unappreciated role for the formin FHOD1 and the small GTPase Rac1 in vaccinia actin tail formation. FHOD1 depletion decreased the number of CEVs forming actin tails and impaired the elongation rate of the formed actin tails. Recruitment of FHOD1 to actin tails relied on its GTPase binding domain in addition to its FH2 domain. In agreement with previous studies showing that FHOD1 is activated by the small GTPase Rac1, Rac1 was enriched and activated at the membrane surrounding actin tails. Rac1 depletion or expression of dominant-negative Rac1 phenocopied the effects of FHOD1 depletion and impaired the recruitment of FHOD1 to actin tails. FHOD1 overexpression rescued the actin tail formation defects observed in cells overexpressing dominant-negative Rac1. Altogether, our results indicate that, to display robust actin-based motility, vaccinia virus integrates the activity of the N-WASP– ARP2/3 and Rac1–FHOD1 pathways.Fil: Alvarez, Diego Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale. School of Medicine; Estados UnidosFil: Agaisse, Herve. University of Yale. School of Medicine; Estados Unido

Decentralized Protection Strategies against SIS Epidemics in Networks

Defining an optimal protection strategy against viruses, spam propagation or any other kind of contamination process is an important feature for designing new networks and architectures. In this work, we consider decentralized optimal protection strategies when a virus is propagating over a network through a SIS epidemic process. We assume that each node in the network can fully protect itself from infection at a constant cost, or the node can use recovery software, once it is infected. We model our system using a game theoretic framework and find pure, mixed equilibria, and the Price of Anarchy (PoA) in several network topologies. Further, we propose both a decentralized algorithm and an iterative procedure to compute a pure equilibrium in the general case of a multiple communities network. Finally, we evaluate the algorithms and give numerical illustrations of all our results.Comment: accepted for publication in IEEE Transactions on Control of Network System

Differential contribution of PB1-F2 to the virulence of highly pathogenic H5N1 influenza A virus in mammalian and avian species

Highly pathogenic avian influenza A viruses (HPAIV) of the H5N1 subtype occasionally transmit from birds to humans and can cause severe systemic infections in both hosts. PB1-F2 is an alternative translation product of the viral PB1 segment that was initially characterized as a pro-apoptotic mitochondrial viral pathogenicity factor. A full-length PB1-F2 has been present in all human influenza pandemic virus isolates of the 20(th) century, but appears to be lost evolutionarily over time as the new virus establishes itself and circulates in the human host. In contrast, the open reading frame (ORF) for PB1-F2 is exceptionally well-conserved in avian influenza virus isolates. Here we perform a comparative study to show for the first time that PB1-F2 is a pathogenicity determinant for HPAIV (A/Viet Nam/1203/2004, VN1203 (H5N1)) in both mammals and birds. In a mammalian host, the rare N66S polymorphism in PB1-F2 that was previously described to be associated with high lethality of the 1918 influenza A virus showed increased replication and virulence of a recombinant VN1203 H5N1 virus, while deletion of the entire PB1-F2 ORF had negligible effects. Interestingly, the N66S substituted virus efficiently invades the CNS and replicates in the brain of Mx+/+ mice. In ducks deletion of PB1-F2 clearly resulted in delayed onset of clinical symptoms and systemic spreading of virus, while variations at position 66 played only a minor role in pathogenesis. These data implicate PB1-F2 as an important pathogenicity factor in ducks independent of sequence variations at position 66. Our data could explain why PB1-F2 is conserved in avian influenza virus isolates and only impacts pathogenicity in mammals when containing certain amino acid motifs such as the rare N66S polymorphism