Detection of Plasmodium spp. in asymptomatic blood donors by the new Brazilian NAT PLUS HIV/HBV/HCV/Malaria Bio-Manguinhos kit.

Background: Transfusion-transmitted malaria (TTM) is a public health problem in endemic and nonendemic areas. The Brazilian Ministry of Health (MH) requested the development of a nucleic acid amplification test (NAT) for the detection of Plasmodium spp. in public blood centers to increase blood safety.

A DNA inducing VLP vaccine designed for HIV and tested in mice.

We developed a DNA vaccine that induces the formation of a VLP in vivo. This VLP was designed to elicit neutralizing antibodies, to induce better T-cell responses and to activate the innate immune system. Overall, 5 groups of 10 mice were electroporated with the following constructs: pVLP-LTR-GagPro [full], pVLP-GagPro [VLP wihout RNA], pVLP-LTR-Gag [VLP immature], pVLP-Gag and pVLP-EnvBG505 [regular DNA vaccine] and a mock group.

Genotypic analysis of the gp41 HR1 region from HIV-1 isolates from enfuvirtide-treated and untreated patients.

Objective: To evaluate the polymorphisms and resistance mutations in gp41 HR1 region of HIV-1.

Methods: The study included 28 HIV-positive patients undergoing enfuvirtide (ENF) treatment or not from Porto Alegre, Rio Grande do Sul state, and Rio de Janeiro, Rio de Janeiro state, between 2006 and 2009. Resistance mutations and polymorphisms of the gp41 HR1 region were detected using the genomic DNA of 12 ENF-untreated patients and 16 patients in ENF treatment, encompassing subtypes B, C, and F1.

Molecular dynamics analysis of HIV-1 matrix protein: clarifying differences between crystallographic and solution structures.

One of the main structural features of the mature HIV-1 virion is the matrix protein (p17). This partially globular protein presents four helixes centrally organized and a fifth one, H5, projecting away from the packed bundle of helixes. Comparison between solution and crystallographic data of p17 indicates a 6 A displacement of a short 3(10) helix and a partial unfolding of H5 in solution related to crystal.

Low accumulation of L90M in protease from subtype F HIV-1 with resistance to protease inhibitors is caused by the L89M polymorphism.

Background: This work evaluates the role of subtype F human immunodeficiency virus type 1 (HIV-1) protease (PR) substitutions L89M and L90M in viral replication and resistance to PR inhibitors (PIs).

Methods: Subtype B and F PR genes were subjected to site-directed mutagenesis, to create and reverse the methionine at positions 89 and 90. Viruses were re-created in cell culture, and their replicative capacity was assessed by fitness assay.

Crystallization of a non-B and a B mutant HIV protease.

HIV polymorphism is responsible for the selection of variant viruses resistant to inhibitors used in AIDS treatment. Knowledge of the mechanism of resistance of those viruses is determinant to the development of new inhibitors able to stop, or at least slow down, the disease's progress caused by new mutations. In this paper, the crystallization and preliminary crystallographic structure solution for two multi-resistant 99 amino acid HIV proteases, both isolated from Brazilian patients failing intensive anti-AIDS therapy are presented, viz.

In vitro hypersusceptibility of human immunodeficiency virus type 1 subtype C protease to lopinavir.

In order to characterize the impact of genetic polymorphisms on the susceptibility of subtype C strains of human immunodeficiency virus type 1 to protease inhibitors (PIs), a subtype B protease that originated from an infectious clone was modified through site-directed mutagenesis to include the amino acid residue signatures of subtype C viruses (I15V, M36I, R41K, H69K, L89 M) with (clone C6) or without (clone C5) an I93L polymorphism present as a molecular signature of the worldwide subtype C protease. Their susceptibilities to commercially available PIs were measured by a recombinant virus phenotyping assay. We could not detect any differences in the 50% inhibitory concentration (IC(50)s) of amprenavir, indinavir, ritonavir, saquinavir, and nelfinavir for the clones analyzed.

Synthesis and anti-HIV activity of new C2 symmetric derivatives designed as HIV-1 protease inhibitors.

The synthesis of several new anti-HIV-1 compounds is described. The new compounds contain a C(2) symmetry axis and a dihidroxyethylene moiety based on the D-tartaric acid back bone. The synthesis of these compounds was achieved in 36-69% overall yields from D-tartaric acid.