ABSTRACT
Existen individuos expuestos repetidamente al virus de la inmunodeficiencia humana (VIH) sin evidencia clínica ni serológica de infección; se denominan expuestos seronegativos (ESN). Se han identificado factores del huésped genéticos e inmunológicos que confieren una baja susceptibilidad a la infección por VIH en ESN. Los factores genéticos están relacionados con genes que codifican los receptores de quimiocinas y sus ligandos naturales, así como los genes del complejo mayor de histocompatibilidad. Los factores inmunológicos se refieren tanto a la inmunidad innata como adaptativa. El estudio de los ESN proporciona una oportunidad única para identificar los posibles mecanismos del huésped implicados en un control eficaz de la infección vírica. Puede ser de gran interés para el diseño de estrategias preventivas o inmuno-terapéuticas, incluyendo vacunas (AU)
Repeated exposure to human immunodeficiency virus (HIV) is not always associated with infection and a subset of individuals remains persistently as HIV-seronegative despite multiple episodes of HIV exposure. These individuals are called HIV-exposed seronegatives (ESN). Several genetic and immunological factors have been involved in this resistance to HIV acquisition. Genetic factors have been linked to genes encoding chemokine receptors and their natural ligands as well as genes of the major histocompatibility complex. Immunological factors include both innate and adaptive immunity. The study of ESN provides a unique opportunity to unveil the mechanisms of natural protection against viral infection. Their better understanding may lead to novel preventive and immune-therapeutic approaches, including vaccines (AU)
Subject(s)
Humans , HIV Infections/transmission , HIV Seronegativity , Immunity, Innate , HIV/pathogenicity , AIDS SerodiagnosisABSTRACT
Repeated exposure to human immunodeficiency virus (HIV) is not always associated with infection and a subset of individuals remains persistently as HIV-seronegative despite multiple episodes of HIV exposure. These individuals are called HIV-exposed seronegatives (ESN). Several genetic and immunological factors have been involved in this resistance to HIV acquisition. Genetic factors have been linked to genes encoding chemokine receptors and their natural ligands as well as genes of the major histocompatibility complex. Immunological factors include both innate and adaptive immunity. The study of ESN provides a unique opportunity to unveil the mechanisms of natural protection against viral infection. Their better understanding may lead to novel preventive and immune-therapeutic approaches, including vaccines.
Subject(s)
Disease Resistance , HIV Infections/immunology , HIV Seronegativity , HIV/immunology , Adaptive Immunity , Disease Resistance/genetics , Disease Resistance/immunology , Genes, MHC Class I , HIV Seronegativity/genetics , HIV Seronegativity/immunology , HumansABSTRACT
INTRODUCTION: In HIV-positive individuals, complex multifactorial mechanisms control viral infection. In addition to viral and immunological factors, the host genetic background also plays an important role. Our objective was to evaluate how various genetic factors associated with delayed AIDS onset. METHODS: Thirty HIV+ long-term nonprogressors (LTNPs) and 30 known progressors were analyzed. Host genes were analyzed in peripheral blood mononuclear cells DNA: CCR5 and HLA were polymerase chain reaction typed. HLA-C5', HCP5 polymorphisms, and CCL3L1 copy number were determined using real-time polymerase chain reaction. RESULTS: The CCL3L1high-copy-CCR5 deletion genetic risk groups was overrepresented in LTNPs. However, separately, neither CCL3L1 nor CCR5 were significantly associated with clinical outcome. HLA seemed as a strong nonprogression determinant, mainly HLA-B and the less-studied HLA-C. HLA-Cw0102 and HLA-C5' had an impact on LTNP phenotype along with HLA-B5701 and B2705. The presence of allele combinations like HLA- B*5701-Cw0602, HLA-B*2705-Cw0102, or HLA-B*3801-Cw1203 had the strongest effect in non-progression. As for HCP5, no independent effect was observed. The studied factors had additive effects, and although the number of patients was small, it seemed that carrying a high number of protective alleles associated with progression delay. CONCLUSIONS: We showed the additive load of protective host factors was predictive of nonprogression, and that HLA-associated factors were predominant in this global effect.
Subject(s)
HIV Infections/genetics , HIV Infections/immunology , HIV Long-Term Survivors , Immunity, Innate , Polymorphism, Genetic , Adult , Chemokines, CC/genetics , Disease Progression , Female , Genotype , HLA Antigens/genetics , Humans , Leukocytes, Mononuclear/immunology , Major Histocompatibility Complex/genetics , Male , Middle Aged , Molecular Sequence Data , RNA, Long Noncoding , RNA, Untranslated , Receptors, CCR5/genetics , Sequence Analysis, DNAABSTRACT
Hepatitis C virus (HCV) infects around 175 million people worldwide and is one of the leading causes of chronic liver disease. Less than one third of patients infected with HCV are able to spontaneously clear the virus during acute infection, while most patients evolve to chronic infection. Control of viral replication has been associated to the cellular component of the host immune response. It is not fully understood what distinguish a successful cellular immune response. An integral interpretation of the numerous experimental findings may allow a better understanding of the immune mechanisms involved in the inability of the immune system to successfully control chronic HCV infection.
