Increased soluble IL-7 receptor concentrations associate with improved IL-7 therapy outcomes in SIV-infected ART-treated Rhesus macaques

The use of interleukin-7 (IL-7) as an immunorestorative therapeutic has proven effective in HIV infection, cancer and bone marrow transplantation. Mediating its activity through membrane-bound IL-7 receptor α (mCD127), IL-7 therapy increases T-cell numbers and survival. A soluble form, sCD127, is found in plasma, and we have previously identified increased plasma sCD127 concentrations in HIV infection. Furthermore, patients with high sCD127 exhibited the best viral control, implicating a role for IL-7 or sCD127 directly in improved viro-logic/immunologic outcomes. The role of the cytokine IL-7 in elevating sCD127 levels was addressed here through assessment of retrospective samples obtained from SIV-infected antiretroviral (ART)-treated Rhesus macaques. IL-7 was administered in clustered weekly doses, allowing for an assessment prior, during and following IL-7 administration. The levels of sCD127 remained relatively unchanged during both early SIV infection and following initiation of ART. However, treatment with IL-7 increased sCD127 concentrations in most animals, transiently or persistently, paralleling increased T-cell numbers, correlating significantly with CD8+ T-cell levels. In addition, proliferating CD4+ or CD8+ T-cells (measured by Ki67) increased in association with elevated sCD127 concentrations. Finally, a high concentration of sCD127 in IL7-treated animals was associated with increased retention of T-cells (measured by BrDU). In addition, a lack, or loss of viral control was associated with more pronounced and frequent elevations in plasma sCD127 concentrations with IL-7 therapy. In summary, plasma sCD127 levels in SIV-infected ART-treated macaques was associated with therapeutic IL-7 administration, with higher sCD127 levels in macaques demonstrating the best T-cell responses. Thi

Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells

SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4+ T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3 +CD4-CD8- T cells (double-negative T cells) partially compensates for CD4+ T cell function in these animals. Passaging plasma from an SIV-infected sooty mangabey with very few CD4 + T cells to SIV-negative animals resulted in rapid loss of CD4 + T cells. Nonetheless, all sooty mangabeys generated SIV-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4- low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4+ T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4+ T cell-like helper functions upon SIV-induced CD4+ T cell depletion in this species

Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1

High-level immune activation and T cell apoptosis represent a hallmark of HIV-1 infection that is absent from nonpathogenic SIV infections in natural primate hosts. The mechanisms causing these varying levels of immune activation are not understood. Here, we report that nef alleles from the great majority of primate lentiviruses, including HIV-2, downmodulate TCR-CD3 from infected T cells, thereby blocking their responsiveness to activation. In contrast, nef alleles from HIV-1 and a subset of closely related SIVs fail to downregulate TCR-CD3 and to inhibit cell death. Thus, Nef-mediated suppression of T cell activation is a fundamental property of primate lentiviruses; that likely evolved to maintain viral persistence in the context of an intact host immune system. This function was lost during viral evolution in a lineage that gave rise to HIV-1 and may have predisposed the simian precursor of HIV-1 for greater pathogenicity in humans

Occurrence of feline immunodeficiency virus infection in cats Ocorrência da infecção pelo vírus da imunodeficiência felina em gatos

The occurrence of feline immunodeficiency virus (FIV) in Brazil has been previously described. This study aimed to investigate the frequency of FIV infection in 454 blood samples from healthy and sick domestic cats from 13 cities of São Paulo State, Brazil as well as to evaluate the risk factors associated with the infection. The results showed that 14.7% (67/454) of the cats were infected with FIV. The clinical evaluation showed that 29.2% of the FIV-positive animals were sick, while 7.3% did not show any type of clinical manifestation. In addition, the vast majority (23.1%) of positive cases corresponded to free-roaming owned cats. The incidence of FIV infection was higher in males (20.3%) than in females (9.7%). The results suggest that certain characteristics such as gender, health status and lifestyle may be associated with the risk of being infected with FIV in the population of cats studied.<br>No Brasil, a ocorrência da infecção pelo vírus da imunodeficiência felina (FIV) já foi descrita. Neste estudo, objetivou-se investigar a freqüência da infecção pelo FIV em 454 amostras de sangue de gatos domésticos doentes e sadios, oriundos de 13 cidades do Estado de São Paulo, assim como avaliar os fatores de risco associados à infecção pelo FIV. Os resultados demonstraram que 14,7% (67/454) dos gatos estavam infectados pelo FIV. A avaliação clínica dos animais investigados mostrou que 29,2% dos animais soropositivos para FIV estavam doentes, enquanto 7,3% não apresentavam nenhuma manifestação clínica. Além disso, a vasta maioria dos animais positivos (23,1%) vivia em residências e tinha livre acesso à rua. A incidência da infecção pelo FIV foi maior nos gatos machos (20,3%) do que nas fêmeas (9,7%). Os resultados sugerem que certas características como sexo, estilo de vida e estado de saúde podem estar associadas ao risco de contrair a infecção pelo FIV na população de gatos estudada

Feline immunodeficiency virusinfection: a comparative study of different diagnostic techniques Infecção pelo vírus da imunodeficiência felina: estudo comparativo de diferentes técnicas de diagnóstico

This study evaluated an indirect immunofluorescence assay (IFA) to detect feline immunodeficiency virus infection (FIV) antibody in a comprehensive epidemiological survey of FIV in Argentina. IFA modified in our laboratory, was compared with two other immunoassays, western blot (WB) and a sandwich immunochromatographic commercial kit (SI), and also with a direct polymerase chain reaction (PCR) method that detects proviral DNA. IFA showed to be a test with high sensitivity and specificity, and could be useful as a diagnostic tool in epidemiological studies. The presence of a low percentage of results with non-specific reactivity in the IFA could be resolved with further testing or use of an alternative method.<br>Avaliou-se a técnica de imunofluorescência indireta (IFA) na detecção de anticorpos contra o vírus da imunodeficiência felina (FIV) numa pesquisa epidemiológica do FIV na Argentina. A IFA foi modificada e comparada com duas outras técnicas imunológicas: western blot (WB) e imunocromatografia em camadas (SI) com kit comercial e também com reação em cadeia de polimerase (PCR) para detecção do DNA proviral. A IFA mostrou ser um teste com alta sensibilidade e especificidade e poderá ser empregada como ferramenta útil em estudos epidemiológicos. A baixa porcentagem de reatividade não específica pode ser esclarecida com testes mais avançados ou usando métodos alternativos