Role of HIV-1 Tat Protein Interactions with Host Receptors in HIV Infection and Pathogenesis.

Each time the virus starts a new round of expression/replication, even under effective antiretroviral therapy (ART), the transactivator of viral transcription Tat is one of the first HIV-1 protein to be produced, as it is strictly required for HIV replication and spreading. At this stage, most of the Tat protein exits infected cells, accumulates in the extracellular matrix and exerts profound effects on both the virus and neighbor cells, mostly of the innate and adaptive immune systems. Through these effects, extracellular Tat contributes to the acquisition of infection, spreading and progression to AIDS in untreated patients, or to non-AIDS co-morbidities in ART-treated individuals, who experience inflammation and immune activation despite virus suppression.

Linear trichoepithelioma on the neck of a 15-year-old girl.

Trichoepitheliomas are trichogenic tumors that can have various clinical morphologies. These tumors are benign and differentiate toward the outer root sheath of the hair follicle. Solitary trichoepitheliomas arise sporadically, in contrast to multiple trichoepitheliomas, which are usually inherited as an autosomal dominant trait or as part of various genetic syndromes.

Biocompatible anionic polymeric microspheres as priming delivery system for effetive HIV/AIDS Tat-based vaccines.

Here we describe a prime-boost regimen of vaccination in Macaca fascicularis that combines priming with novel anionic microspheres designed to deliver the biologically active HIV-1 Tat protein and boosting with Tat in Alum. This regimen of immunization modulated the IgG subclass profile and elicited a balanced Th1-Th2 type of humoral and cellular responses. Remarkably, following intravenous challenge with SHIV89.

A combination HIV vaccine based on Tat and Env proteins was immunogenic and protected macaques from mucosal SHIV challenge in a pilot study.

HIV native Tat and V2 loop-deleted Env (EnvΔV2) proteins already proved safe and immunogenic in phase I clinical testing as single vaccine components. Further, a phase II vaccine trial with Tat showed intensification of the therapeutic effects of HAART in successfully treated HIV-infected individuals. Here a pilot study assessed the immunogenicity and protective efficacy of an HIV/AIDS vaccine based on the combination of Tat and EnvΔV2 proteins in cynomolgus macaques against homologous intrarectal challenge with 35 MID(50) (monkey infectious dose 50) of an R5 simian-human immunodeficiency virus (SHIV(SF162P4cy)).

Eruptive xanthomas as a cutaneous manifestation of hypertriglyceridemia: a case report.

A 28-year-old veteran presented to the Wilford Hall dermatology clinic in San Antonio, Texas, with a six-month history of a rash that his primary care physician diagnosed as molluscum contagiosum. The rash consisted of clusters of 3 to 6mm yellowish papules with erythematous borders that concentrated on the extensor surfaces of his extremities, lower back, and buttocks. A biopsy determined that the patient had a case of eruptive xanthoma.

Containment of infection in tat vaccinated monkeys after rechallenge with a higher dose of SHIV89.6P(cy243).

We previously reported that cynomolgus monkeys vaccinated with the human immunodeficiency virus (HIV)-1 Tat protein controlled infection after challenge with the simian human immunodeficiency virus (SHIV) 89.6P(cy243) for up to 2 y of follow-up. To evaluate the breadth of the protective immunity elicited by the Tat protein, the vaccines along with the naïve monkeys were intravenously rechallenged with a fivefold higher dose (50 MID(50)) of the same SHIV-89.

Multiprotein genetic vaccine in the SIV-Macaca animal model: a promising approach to generate sterilizing immunity to HIV infection.

Background: Vaccine combining structural and regulatory proteins is an emerging approach to develop an HIV/AIDS vaccine and therefore, the immunogenicity and efficacy of two regimens of immunization combining structural (Gag/Pol, Env) and regulatory (Rev, Tat, Nef) Simian immunodeficiency virus (SIV) proteins were compared in cynomolgus monkeys.

Methods: Monkeys were immunized with Modified Vaccine Ankara vector (MVA-J5) (protocol 1) or with DNA, Semliki forest virus and MVA vectors (DNA/SFV/MVA) (protocol 2). At week 32, all monkeys were challenge intravenously (protocol 1) or intrarectally (protocol 2) with 50 MID(50) of SIVmac251.

Characterization of alpha-defensins plasma levels in Macaca fascicularis and correlations with virological parameters during SHIV89.6Pcy11 experimental infection.

Alpha-defensins have been shown to inhibit HIV-1 replication in vitro and may contribute to the overall control of viral replication in vivo. In the present work, we quantitatively measured the levels of alpha-defensins in the plasma of healthy and experimentally SHIV-infected Macaca fascicularis (cynomolgus monkeys), an animal model of AIDS pathogenesis and vaccine development. Characterization of physiological plasma alpha-defensins levels was performed in 12 healthy monkeys following longitudinal analysis using an alpha-defensins ELISA kit currently validated for macaque use.

T-cell-mediated protective efficacy of a systemic vaccine approach in cynomolgus monkeys after SIV mucosal challenge.

The immunogenicity and the protective efficacy of a new polyvalent triple vector (DNA/SFV/MVA) based vaccine against mucosal challenge with pathogenic SIVmac251 were investigated. Cynomolgus monkeys (Macaca fascicularis) were primed intradermally with DNA, boosted twice subcutaneously with recombinant Semliki Forest virus (rSFV) and finally intramuscularly with recombinant Modified Vaccinia Virus Ankara strain (rMVA). Both DNA and recombinant viral vectors expressed SIV proteins (Gag, Pol, Tat, Rev, Nef and Env).

Protective efficacy of a multicomponent vector vaccine in cynomolgus monkeys after intrarectal simian immunodeficiency virus challenge.

We investigated the protective efficacy of a systemic triple vector (DNA/rSFV/rMVA)-based vaccine against mucosal challenge with pathogenic simian immunodeficiency virus (SIV) in cynomolgus monkeys. Animals were immunized at week 0 with DNA (intradermally), at weeks 8 and 16 with recombinant Semliki Forest virus (rSFV, subcutaneously) and finally, at week 24, with recombinant modified vaccinia virus Ankara strain (rMVA, intramuscularly). Both DNA and recombinant viral vectors expressed a wide range of SIV proteins (Gag, Pol, Tat, Rev, Env and Nef).