Monocytes Contribute to Differential Immune Pressure on R5 versus X4 HIV through the Adipocytokine Visfatin/NAMPT

Background: The immune system exerts a diversifying selection pressure on HIV through cellular, humoral and innate mechanisms. This pressure drives viral evolution throughout infection. A better understanding of the natural immune pressure on the virus during infection is warranted, given the clinical interest in eliciting and sustaining an immune response to HIV which can help to control the infection. We undertook to evaluate the potential of the novel HIV-induced, monocyte-derived factor visfatin to modulate viral infection, as part of the innate immune pressure on viral populations. Results: We show that visfatin is capable of selectively inhibiting infection by R5 HIV strains in macrophages and resting PBMC in vitro, while at the same time remaining indifferent to or even favouring infection by X4 strains. Furthermore, visfatin exerts a direct effect on the relative fitness of R5 versus X4 infections in a viral competition setup. Direct interaction of visfatin with the CCR5 receptor is proposed as a putative mechanism for this differential effect. Possible in vivo relevance of visfatin induction is illustrated by its association with the dominance of CXCR4-using HIV in the plasma. Conclusions: As an innate factor produced by monocytes, visfatin is capable of inhibiting infections by R5 but not X4 strains, reflecting a potential selective pressure against R5 viruses. © 2012 Van den Bergh et al.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Punica granatum (Pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide

BACKGROUND: For ≈ 24 years the AIDS pandemic has claimed ≈ 30 million lives, causing ≈ 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic. Antiretroviral chemotherapeutics have decreased AIDS mortality in industrialized countries, but only minimally in developing countries. To prevent an analogous dichotomy, microbicides should be: acceptable; accessible; affordable; and accelerative in transition from development to marketing. Already marketed pharmaceutical excipients or foods, with established safety records and adequate anti-HIV-1 activity, may provide this option. METHODS: Fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The best juice was tested for inhibition of: (1) infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor; and (2) binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5. To remove most colored juice components, the adsorption of the effective ingredient(s) to dispersible excipients and other foods was investigated. A selected complex was assayed for inhibition of infection by primary HIV-1 isolates. RESULTS: HIV-1 entry inhibitors from pomegranate juice adsorb onto corn starch. The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O. CONCLUSION: These results suggest the possibility of producing an anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety has been established throughout centuries, provided that its quality is adequately standardized and monitored

Secure Code Updates for Smart Embedded Devices based on PUFs

Code update is a very useful tool commonly used in low-end embedded devices to improve the existing functionalities or patch discovered bugs or vulnerabilities. If the update protocol itself is not secure, it will only bring new threats to embedded systems. Thus, a secure code update mechanism is required. However, existing solutions either rely on strong security assumptions, or result in considerable storage and computation consumption, which are not practical for resource-constrained embedded devices (e.g., in the context of Internet of Things). In this work, we propose to use intrinsic device characteristics (i.e., Physically Unclonable Functions or PUF) to design a practical and lightweight secure code update scheme. Our scheme can not only ensure the freshness, integrity, confidentiality and authenticity of code update, but also verify that the update is installed correctly on a specific device without any malicious software. Cloned or counterfeit devices can be excluded as the code update is bound to the unpredictable physical properties of underlying hardware. Legitimate devices in an untrustworthy software state can be restored by filling suspect memory with PUF-derived random numbers. After update installation, the initiator of the code update is able to obtain the verifiable software state from device, and the device can maintain a sustainable post-update secure check by enforcing a secure call sequence. To demonstrate the practicality and feasibility, we also implement the proposed scheme on a low-end MCU platform (TI MSP430) by using onboard SRAM and Flash resources

A Fourier Analysis Based Attack against Physically Unclonable Functions

Electronic payment systems have leveraged the advantages offered by the RFID technology, whose security is promised to be improved by applying the notion of Physically Unclonable Functions (PUFs). Along with the evolution of PUFs, numerous successful attacks against PUFs have been proposed in the literature. Among these are machine learning (ML) attacks, ranging from heuristic approaches to provable algorithms, that have attracted great attention. Our paper pursues this line of research by introducing a Fourier analysis based attack against PUFs. More specifically, this paper focuses on two main aspects of ML attacks, namely being provable and noise tolerant. In this regard, we prove that our attack is naturally integrated into a provable Probably Approximately Correct (PAC) model. Moreover, we show that our attacks against known PUF families are effective and applicable even in the presence of noise. Our proof relies heavily on the intrinsic properties of these PUF families, namely arbiter, Ring Oscillator (RO), and Bistable Ring (BR) PUF families. We believe that our new style of ML algorithms, which take advantage of the Fourier analysis principle, can offer better measures of PUF security

Elicitation of Neutralizing Antibodies Directed against CD4-Induced Epitope(s) Using a CD4 Mimetic Cross-Linked to a HIV-1 Envelope Glycoprotein

The identification of HIV-1 envelope glycoprotein (Env) structures that can generate broadly neutralizing antibodies (BNAbs) is pivotal to the development of a successful vaccine against HIV-1 aimed at eliciting effective humoral immune responses. To that end, the production of novel Env structure(s) that might induce BNAbs by presentation of conserved epitopes, which are otherwise occluded, is critical. Here, we focus on a structure that stabilizes Env in a conformation representative of its primary (CD4) receptor-bound state, thereby exposing highly conserved “CD4 induced” (CD4i) epitope(s) known to be important for co-receptor binding and subsequent virus infection. A CD4-mimetic miniprotein, miniCD4 (M64U1-SH), was produced and covalently complexed to recombinant, trimeric gp140 envelope glycoprotein (gp140) using site-specific disulfide linkages. The resulting gp140-miniCD4 (gp140-S-S-M64U1) complex was recognized by CD4i antibodies and the HIV-1 co-receptor, CCR5. The gp140-miniCD4 complex elicited the highest titers of CD4i binding antibodies as well as enhanced neutralizing antibodies against Tier 1 viruses as compared to gp140 protein alone following immunization of rabbits. Neutralization against HIV-27312/V434M and additional serum mapping confirm the specific elicitation of antibodies directed to the CD4i epitope(s). These results demonstrate the utility of structure-based approach in improving immunogenic response against specific region, such as the CD4i epitope(s) here, and its potential role in vaccine application

HIV interactions with monocytes and dendritic cells: viral latency and reservoirs

HIV is a devastating human pathogen that causes serious immunological diseases in humans around the world. The virus is able to remain latent in an infected host for many years, allowing for the long-term survival of the virus and inevitably prolonging the infection process. The location and mechanisms of HIV latency are under investigation and remain important topics in the study of viral pathogenesis. Given that HIV is a blood-borne pathogen, a number of cell types have been proposed to be the sites of latency, including resting memory CD4+ T cells, peripheral blood monocytes, dendritic cells and macrophages in the lymph nodes, and haematopoietic stem cells in the bone marrow. This review updates the latest advances in the study of HIV interactions with monocytes and dendritic cells, and highlights the potential role of these cells as viral reservoirs and the effects of the HIV-host-cell interactions on viral pathogenesis

Setting the stage: host invasion by HIV.

For more than two decades, HIV has infected millions of people worldwide each year through mucosal transmission. Our knowledge of how HIV secures a foothold at both the molecular and cellular levels has been expanded by recent investigations that have applied new technologies and used improved techniques to isolate ex vivo human tissue and generate in vitro cellular models, as well as more relevant in vivo animal challenge systems. Here, we review the current concepts of the immediate events that follow viral exposure at genital mucosal sites where most documented transmissions occur. Furthermore, we discuss the gaps in our knowledge that are relevant to future studies, which will shape strategies for effective HIV prevention

Population genomics of sub-Saharan Drosophila melanogaster: African diversity and non-African admixture

(ABRIDGED) We report the genome sequencing of 139 wild-derived strains of D. melanogaster, representing 22 population samples from the sub-Saharan ancestral range of this species, along with one European population. Most genomes were sequenced above 25X depth from haploid embryos. Results indicated a pervasive influence of non-African admixture in many African populations, motivating the development and application of a novel admixture detection method. Admixture proportions varied among populations, with greater admixture in urban locations. Admixture levels also varied across the genome, with localized peaks and valleys suggestive of a non-neutral introgression process. Genomes from the same location differed starkly in ancestry, suggesting that isolation mechanisms may exist within African populations. After removing putatively admixed genomic segments, the greatest genetic diversity was observed in southern Africa (e.g. Zambia), while diversity in other populations was largely consistent with a geographic expansion from this potentially ancestral region. The European population showed different levels of diversity reduction on each chromosome arm, and some African populations displayed chromosome arm-specific diversity reductions. Inversions in the European sample were associated with strong elevations in diversity across chromosome arms. Genomic scans were conducted to identify loci that may represent targets of positive selection. A disproportionate number of candidate selective sweep regions were located near genes with varied roles in gene regulation. Outliers for Europe-Africa FST were found to be enriched in genomic regions of locally elevated cosmopolitan admixture, possibly reflecting a role for some of these loci in driving the introgression of non-African alleles into African populations

Compact implementations of pairings

Contains fulltext : 75347.pdf (preprint version ) (Open Access)Alleen electronisch beschikbaar4th Benelux Workshop on Information and System Security - WISSec 2009, November 19-20, 2009, Louvain-la-Neuve, Belgium., 19 november 200915 p

LiBrA-CAN: A lightweight broadcast authentication protocol for controller area networks

Security in vehicular networks established itself as a highly active research area in the last few years. However, there are only a few results so far on assuring security for communication buses inside vehicles. Here we advocate the use of a protocol based entirely on simple symmetric primitives that takes advantage of two interesting procedures which we call key splitting and MAC mixing. Rather than achieving authentication independently for each node, we split authentication keys between groups of multiple nodes. This leads to a more efficient progressive authentication that is effective especially in the case when compromised nodes form only a minority and we believe such an assumption to be realistic in automotive networks. To gain more security we also account an interesting construction in which message authentication codes are amalgamated using systems of linear equations. We study several protocol variants which are extremely flexible allowing different trade-offs on bus load, computational cost and security level. Experimental results are presented on state-of-the-art Infineon TriCore controllers which are contrasted with low end controllers with Freescale S12X cores, all these devices are wide spread in the automotive industry. Finally, we discuss a completely backward compatible solution based on CAN+, a recent improvement of CAN. © Springer-Verlag 2012.status: publishe