Human immunodeficiency virus interactions with CD8+ T lymphocytes.

Human immunodeficiency virus (HIV)-specific CD8+ T cells can mediate anti-HIV activity by both cytolytic (cytotoxic T lymphocyte or CTL) and non-cytolytic mechanisms (antiviral) and play a crucial role in HIV pathogenesis. Both mechanisms actively contribute to the control of HIV in vivo. The non-cytolytic CD8+T cells from individuals infected with HIV suppress virus replication in CD4+ T cells in vitro by a non-cytolytic mechanism that involves interplay of several chemokines and an unidentified secreted soluble CD8 (+)-cell antiviral factor (CAF).

Preserved central memory and activated effector memory CD4+ T-cell subsets in human immunodeficiency virus controllers: an ANRS EP36 study.

Human immunodeficiency virus (HIV) controllers are rare individuals who spontaneously control HIV type 1 replication for 10 years or more in the absence of antiretroviral treatment. In the present study, HIV controllers (n = 11) maintained potent HIV-specific CD4 responses in spite of very low antigenic loads. Their CD4+ central memory T (T(CM)) cells were characterized by near-normal numbers and preserved interleukin-2 (IL-2) secretion in response to HIV antigens and uniformly high expression of the survival receptor IL-7 receptor alpha (IL-7Ralpha).

Genetic analyses reveal structured HIV-1 populations in serially sampled T lymphocytes of patients receiving HAART.

HIV-1 infection and compartmentalization in diverse leukocyte targets significantly contribute to viral persistence during suppressive highly active antiretroviral therapy (HAART). Longitudinal analyses were performed on envelope sequences of HIV-1 populations from plasma, CD4+ and CD8+ T lymphocytes in 14 patients receiving HAART and 1 therapy-naive individual. Phylogenetic reconstructions and analysis of molecular variance revealed that HIV-1 populations in CD4+ and CD8+ T cells remained compartmentalized over time in most individuals.

Assessment of drug resistance mutations in plasma and peripheral blood mononuclear cells at different plasma viral loads in patients receiving HAART.

Background: HIV drug resistance mutations both in peripheral blood mononuclear cells (PBMCs) and plasma have the ability to influence the outcome of highly active antiretroviral therapy for HIV patients. PBMCs harbor archival proviral DNA, are a major source of HIV and also underdo latent infection during suppressive HAART.

Objectives: The main objectives of this study were to assess whether specific viral load groups are better predictors of drug resistance and to examine the utility of PBMCs for drug resistance testing during HAART.

Rapid and sensitive detection of severe acute respiratory syndrome coronavirus by rolling circle amplification.

The severe acute respiratory syndrome (SARS) epidemic of 2003 was responsible for 774 deaths and caused significant economic damage worldwide. Since July 2003, a number of SARS cases have occurred in China, raising the possibility of future epidemics. We describe here a rapid, sensitive, and highly efficient assay for the detection of SARS coronavirus (SARS-CoV) in cultured material and a small number (n = 7) of clinical samples.

Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19.

Hartnup disorder (OMIM 234500) is an autosomal recessive abnormality of renal and gastrointestinal neutral amino acid transport noted for its clinical variability. We localized a gene causing Hartnup disorder to chromosome 5p15.33 and cloned a new gene, SLC6A19, in this region.

Obstacles to successful antiretroviral treatment of HIV-1 infection: problems & perspectives.

Mutations in human immunodeficiency virus type 1 (HIV-1) are a major impediment to successful highly active antiretroviral therapy (HAART) and the design of anti-HIV vaccines. Although HAART has made long-term suppression of HIV a reality, drug resistance, drug toxicity, drug penetration, adherence to therapy, low levels of continued viral replication in cellular reservoirs and augmentation of host immune responses are some of the most important challenges that remain to be sorted out. Continuing viral replication in the face of HAART leads to the accumulation of drug resistance mutations, increase in viral loads and eventual disease progression.

HIV-1 compartmentalization in diverse leukocyte populations during antiretroviral therapy.

CD4+ T lymphocytes are the primary target of human immunodeficiency virus type 1 (HIV-1), but there is increasing evidence that other immune cells in the blood, including CD8+ T lymphocytes and monocytes, are also productively infected. The extent to which these additional cellular reservoirs contribute to ongoing immunodeficiency and viral persistence during therapy remains unclear. In this study, we conducted a detailed investigation of HIV-1 diversity and genetic structure in CD4+ T cells, CD8+ T cells, and monocytes of 13 patients receiving highly active antiretroviral therapy (HAART).

Reservoirs of HIV-1 in vivo: implications for antiretroviral therapy.

The eradication of HIV-1 from infected individuals remains the ultimate goal of all anti-HIV therapeutics. Although highly active antiretroviral therapy (HAART) has led to a profound decrease in morbidity and mortality in infected people by suppressing HIV replication, the virus continues to evolve slowly during therapy even when patients achieve below detectable levels of HIV in plasma. HIV-1 persists in latently infected memory CD4+ T cells and there is minimal decay of HIV in this compartment despite prolonged HAART.

Differential cellular distribution of HIV-1 drug resistance in vivo: evidence for infection of CD8+ T cells during HAART.

This study presents a detailed analysis of HIV-1 populations isolated from total PBMC, plasma, CD4+ T cells, CD8+ T cells, and monocytes/macrophages in 13 patients receiving HAART. Sequence analysis of the reverse transcriptase and protease genes indicated that viral strains isolated from different blood leukocytes were genetically distinct in each subject. Notably, HIV variants isolated from CD8+ T cells were distantly related to strains derived from other blood cell types, providing evidence for the strain-specific infection of CD8+ T cells in vivo.