%0 Journal Article %J Curr HIV Res %D 2015 %T Meta-analysis and time series modeling allow a systematic review of primary HIV-1 drug-resistant prevalence in Latin America and Caribbean. %A Coelho, Antônio Victor Campos %A De Moura, Ronald Rodrigues %A da Silva, Ronaldo Celerino %A Kamada, Anselmo Jiro %A Guimarães, Rafael Lima %A Brandão, Lucas André Cavalcanti %A Coelho, Hemílio Fernandes Campos %A Crovella, Sergio %X

Here we review the prevalence of HIV-1 primary drug resistance in Latin America and Caribbean using meta-analysis as well as time-series modeling. We also discuss whether there could be a drawback to HIV/AIDS programs due to drug resistance in Latin America and Caribbean in the next years. We observed that, although some studies report low or moderate primary drug resistance prevalence in Caribbean countries, this evidence needs to be updated. In other countries, such as Brazil and Argentina, the prevalence of drug resistance appears to be rising. Mutations conferring resistance against reverse transcriptase inhibitors were the most frequent in the analyzed populations (70% of all mutational events). HIV-1 subtype B was the most prevalent in Latin America and the Caribbean, although subtype C and B/F recombinants have significant contributions in Argentina and Brazil. Thus, we suggest that primary drug resistance in Latin America and the Caribbean could have been underestimated. Clinical monitoring should be improved to offer better therapy, reducing the risk for HIV-1 resistance emergence and spread, principally in vulnerable populations, such as men who have sex with men transmission group, sex workers and intravenous drug users.

%B Curr HIV Res %V 13 %P 125-42 %8 2015 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/25777517?dopt=Abstract %0 Journal Article %J Mol Biol Rep %D 2014 %T Association of CD209 and CD209L polymorphisms with tuberculosis infection in a Northeastern Brazilian population. %A da Silva, Ronaldo Celerino %A Segat, Ludovica %A da Cruz, Heidi Lacerda Alves %A Schindler, Haiana Charifker %A Montenegro, Lilian Maria Lapa %A Crovella, Sergio %A Guimarães, Rafael Lima %K Adult %K Alleles %K Brazil %K Case-Control Studies %K Cell Adhesion Molecules %K Dendritic Cells %K Female %K Genetic Predisposition to Disease %K Haplotypes %K Humans %K Lectins, C-Type %K Male %K Mycobacterium tuberculosis %K Polymorphism, Single Nucleotide %K Promoter Regions, Genetic %K Receptors, Cell Surface %K Tuberculosis %K Young Adult %X

Tuberculosis (TB) caused by Mycobacterium tuberculosis, is major cause of morbidity and mortality worldwide. So far, many candidate genes have been investigated for their possible association with TB. Dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) and Liver/lymph node-specific intercellular adhesion molecule-grabbing non-integrin (L-SIGN), encoded by CD209 and CD209L genes respectively, are known for binding to M. tuberculosis on human dendritic cells and macrophages. We screened 4 single nucleotide polymorphisms (SNPs) in the promoter region of CD209, namely -939G>A (rs735240), -871A>G (rs735239), -336A>G (rs4804803) and -139G>A (rs2287886) and tandem repeat polymorphisms in exon 4 of CD209 and CD209L genes looking for association with TB in a Northeastern Brazilian population (295 subjects, 131 TB patients and 164 healthy controls). The -139G>A and -939G>A SNPs were associated with susceptibility to TB, and in particular with pulmonary and extra-pulmonary forms respectively. The -871A>G and -336A>G SNPs were associated, the first with protection to both pulmonary and extra-pulmonary TB, the latter only with the pulmonary form. An association between GGAG haplotype and protection to TB infection was also found. Also tandem repeat polymorphism in CD209L exon 4 was associated with TB infection. This study provides evidence of an association between CD209 and CD209L polymorphisms and TB development in a Brazilian population, suggesting that variations in these genes may influence the protection and susceptibility to infection caused by M. tuberculosis.

%B Mol Biol Rep %V 41 %P 5449-57 %8 2014 Aug %G eng %N 8 %1 http://www.ncbi.nlm.nih.gov/pubmed/24874302?dopt=Abstract %R 10.1007/s11033-014-3416-y %0 Journal Article %J Immunobiology %D 2014 %T DC-SIGN polymorphisms are associated to type 1 diabetes mellitus. %A da Silva, Ronaldo Celerino %A Cunha Tavares, Nathália de Alencar %A Moura, Ronald %A Coelho, Antônio %A Guimarães, Rafael Lima %A Araújo, Jacqueline %A Crovella, Sergio %A Brandão, Lucas André Cavalcanti %A Silva, Jaqueline de Azevêdo %K Adolescent %K Alleles %K Case-Control Studies %K Cell Adhesion Molecules %K Child %K Child, Preschool %K Diabetes Mellitus, Type 1 %K Female %K Gene Frequency %K Genetic Association Studies %K Genetic Predisposition to Disease %K Genotype %K Humans %K Infant %K Infant, Newborn %K Lectins, C-Type %K Male %K Odds Ratio %K Polymorphism, Genetic %K Polymorphism, Single Nucleotide %K Promoter Regions, Genetic %K Receptors, Cell Surface %X

Type I diabetes mellitus (T1DM) is an autoimmune disorder featured by raised glucoses levels. It has been hypothesised that raised glucose levels in T1DM might be recognised as PAMPs, leading to immune response by overloading the cell receptors for pathogens recognition. DC-SIGN is a transmembrane protein, present in dendritic cells (DC) and macrophages: it has an important role in inflammatory response and T cells activation. Notably, DC-SIGN activation and triggering of the immune response depend on the type of ligand, which may lead to a pro or anti-inflammatory pathway. In our association study, we analysed the SNPs rs4804803 (-336 A>G) and rs735239 (-871 A>G), both at DC-SIGN promoter region, in 210 T1DM patients and 157 healthy controls, also looking for a correlation with the age of onset of the disease. We found that the allele G and genotypes G/G and A/G of SNP-871 (rs735239), as well as the alleles G-G (rs735239-rs4804803) and genotypes combined AA-GG (rs735239-rs4804803) were associated with protection of T1DM development. We did not find association between these variations with the age of onset of the disease and the presence of other autoimmune disorders. Our results suggest that SNPs in DC-SIGN promoter region can be associated to protection for T1DM in the Northeast Brazilian population.

%B Immunobiology %V 219 %P 859-65 %8 2014 Nov %G eng %N 11 %1 http://www.ncbi.nlm.nih.gov/pubmed/25092567?dopt=Abstract %R 10.1016/j.imbio.2014.07.011 %0 Journal Article %J Hum Immunol %D 2012 %T Polymorphisms in DC-SIGN and L-SIGN genes are associated with HIV-1 vertical transmission in a Northeastern Brazilian population. %A da Silva, Ronaldo Celerino %A Segat, Ludovica %A Zanin, Valentina %A Arraes, Luiz Claudio %A Crovella, Sergio %K Alleles %K Brazil %K Cell Adhesion Molecules %K Child %K Child, Preschool %K Exons %K Female %K Gene Frequency %K Genotype %K HIV Infections %K HIV-1 %K Humans %K Infectious Disease Transmission, Vertical %K Lectins, C-Type %K Male %K Polymorphism, Single Nucleotide %K Promoter Regions, Genetic %K Receptors, Cell Surface %K Tandem Repeat Sequences %X

DC-SIGN and L-SIGN are receptors expressed on specialized macrophages in decidua, (Hofbauer and placental capillary endothelial cells), known to interact with several pathogens, including HIV-1. To disclose the possible involvement of these molecules in the susceptibility to HIV vertical transmission, we analyzed DC-SIGN and L-SIGN gene single nucleotide polymorphisms (SNPs) in 192 HIV-1 positive children and 58 HIV-1 negative children all born to HIV-1 positive mothers, as well as 96 healthy uninfected children not exposed to HIV-1, all from Northeast Brazil. The frequency of three SNPs in the DC-SIGN promoter (-139G>A, -201G>T and -336A>G) were significantly different when comparing HIV positive children with HIV-1 exposed uninfected children, indicating an association with susceptibility to HIV-1 vertical transmission. This genetic association suggests that DC-SIGN molecule may play a role in susceptibility to HIV-1 infection through vertical transmission.

%B Hum Immunol %V 73 %P 1159-65 %8 2012 Nov %G eng %N 11 %1 http://www.ncbi.nlm.nih.gov/pubmed/22902397?dopt=Abstract %R 10.1016/j.humimm.2012.07.338 %0 Journal Article %J Hum Immunol %D 2011 %T Role of DC-SIGN and L-SIGN receptors in HIV-1 vertical transmission. %A da Silva, Ronaldo Celerino %A Segat, Ludovica %A Crovella, Sergio %K Cell Adhesion Molecules %K HIV Infections %K HIV-1 %K Humans %K Immunity, Innate %K Infectious Disease Transmission, Vertical %K Lectins, C-Type %K Polymorphism, Genetic %K Receptors, Cell Surface %X

The innate immune system acts in the first line of host defense against pathogens. One of the mechanisms used involves the early recognition and uptake of microbes by host professional phagocytes, through pattern recognition receptors (PRRs). These PRRs bind to conserved microbial ligands expressed by pathogens and initiate both innate and adaptative immune responses. Some PRRs located on the surface of dendritic cells (DCs) and other cells seem to play an important role in human immunodeficiency virus type 1 (HIV-1) transmission. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin, CD209 (DC-SIGN) and its homolog, DC-SIGN-related (DC-SIGNR or L-SIGN) receptors are PPRs able to bind the HIV-1 gp120 envelope protein and, because alterations in their expression patterns also occur, they might play a role in both horizontal and vertical transmission as well as in disseminating the virus within the host. This review aims to explore the involvement of the DC-SIGN and L-SIGN receptors in HIV-1 transmission from mother to child.

%B Hum Immunol %V 72 %P 305-11 %8 2011 Apr %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/21277928?dopt=Abstract %R 10.1016/j.humimm.2011.01.012