Analysis of full-length mitochondrial DNA D-loop sequences from Macaca fascicularis of different geographical origin reveals novel haplotypes.

BACKGROUND: Cynomolgus macaques are indigenous to Asia occupying a range of geographical areas. A non-indigenous population established on Mauritius approximately 500 years ago. Mauritian cynomolgus macaques are recognised as having low genetic diversity compared to Indonesian macaques, from which they originated. As cynomolgus macaques are widely used as a biomedical model, there have been many studies of their genetic relationships. However, population diversity and relationships have only been assessed through analysis of either the hypervariable region I or II separately within the D-loop region of the mitochondrial genome in these macaques. METHODS: Using sequencing, we defined haplotypes encompassing the full D-loop sequence for Mauritian and Indonesian cynomolgus macaques. RESULTS: We evaluated the haplotype relationships by constructing a median-joining network based on full-length D-loop sequences, which has not been reported previously. CONCLUSION: Our data allow a complete D-loop haplotype, including a hereto unreported polymorphic region, to be defined to aid the resolution of populations of cynomolgus macaques and which highlights the value in analysing both D-loop hypervariable regions in concert.

Changes in immune cell populations in the periphery and liver of GBV-B-infected and convalescent tamarins (Saguinus labiatus).

Flaviviruses related to hepatitis C virus (HCV) in suitable animal models may provide further insight into the role that cellular immunity contributes to spontaneous clearance of HCV. We characterised changes in lymphocyte populations in tamarins with an acute GBV-B infection, a hepatitis virus of the flaviviridae. Major immune cell populations were monitored in peripheral and intra-hepatic lymphocytes at high viraemia or following a period when peripheral virus was no longer detected. Limited changes in major lymphocyte populations were apparent during high viraemia; however, the proportions of CD3(+) lymphocytes decreased and CD20(+) lymphocytes increased once peripheral viraemia became undetectable. Intrahepatic lymphocyte populations increased at both time points post-infection. Distinct expression patterns of PD-1, a marker of T-cell activation, were observed on peripheral and hepatic lymphocytes; notably there was elevated PD-1 expression on hepatic CD4(+) T-cells during high viraemia, suggesting an activated phenotype, which decreased following clearance of peripheral viraemia. At times when peripheral vRNA was not detected, suggesting viral clearance, we were able to readily detect GBV-B RNA in the liver, indicative of long-term virus replication. This study is the first description of changes in lymphocyte populations during GBV-B infection of tamarins and provides a foundation for more detailed investigations of the responses that contribute to the control of GBV-B infection.

Horizontal acquisition and a broad biodistribution typify simian foamy virus infection in a cohort of Macaca fascicularis.

BACKGROUND: Foamy viruses are non-pathogenic in vivo and naturally infect all species of non-human primates (NHP). Simian foamy viruses (SFV) are highly prevalent in both free ranging and captive NHP but few longitudinal studies have been performed to assess the prevalence and biodistribution of SFV within captive NHP. METHOD: LTR and pol gene along with Gag antibody detection were undertaken to identify infection in a cohort of over 80 captive macaques. RESULTS: The prevalence of SFV was between 64% and 94% in different groups. Access to 23 dam-infant pairs allowed us to reveal horizontal transfer as the dominant route of SFV transmission in our cohort. Further, analysis of SFV from a range of tissues and blood revealed that macaques as young as six months old can be infected and that proviral biodistribution increases with age. CONCLUSIONS: These are the first data of this type for a captive cohort of cynomolgus macaques.

Simian T-cell lymphotropic virus type I alters the proviral load and biodistribution of simian retrovirus type 2 in co-infected macaques, supporting advancement of immunosuppressive pathology.

The infection dynamics and pathology of a retrovirus may be altered by one or more additional viruses. To investigate this further, this study characterized proviral load, biodistribution and the immune response in Macaca fascicularis naturally infected with combinations of simian retrovirus type 2 (SRV-2) and simian T-cell lymphotropic virus type I (STLV-I). As the mesenteric lymph node (MLN) and the spleen have been implicated previously in response to retroviral infection, the morphology and immunopathology of these tissues were assessed. The data revealed a significant change in SRV-2 biodistribution in macaques infected with STLV-I. Pathological changes were greater in the MLN and spleen of STLV-I-infected and co-infected macaques compared with the other groups. Immune-cell populations in co-infected macaque spleens were increased and there was an atypical distribution of B-cells. These findings suggest that the infection dynamics of each virus in a co-infected individual may be affected to a different extent and that STLV-I appears to be responsible for enhancing the biodistribution and associated pathological changes in SRV-2 in macaques.

Characterisation of MHC haplotypes in a breeding colony of Indonesian cynomolgus macaques reveals a high level of diversity.

Recent reports have revealed that cynomolgus macaques obtained from different geographic origins may be more or less suitable for particular studies depending on the specific question(s) being addressed, e.g. Mauritian cynomolgus macaques are particularly suitable for detailed immunological studies against a limited genetic background while less conserved populations may be more appropriate to predict breadth of vaccine coverage in the genetically diverse human population. We have characterised MHC haplotypes in 90 Indonesian cynomolgus macaques using microsatellite and reference strand conformational analysis. Thirty unique haplotypes were defined in the cohort, emphasising the high degree of diversity in this population of cynomolgus macaques. The majority of haplotypes were present at a frequency of ≤ 6%. Transcription profiles indicated that each haplotype was associated with two to eight transcribed class I alleles. The results corroborate previous reports of the extensive MHC diversity of Indonesian cynomolgus macaques and provide additional data to inform colony management decisions. Further, definition of the MHC diversity of the population satisfies one of the prerequisites to MHC association studies and detailed immunological investigations in this outbred non-human primate species.

Mechanisms of protection induced by attenuated simian immunodeficiency virus.

To determine whether attenuated simian immunodeficiency virus (SIV) vaccines confer protection against superinfection via secondary cellular immune responses, we searched for markers of immune activation following rechallenge. Productive infection with either attenuated SIVmacC8 or wild-type SIVmacJ5 resulted in a transient increase in T-lymphocyte CD25 and Mafa-DR expression. A pronounced increase in the frequency of FAS+ CD8+ lymphocytes was observed following SIVmacJ5 infection only. A transient increase in lymphocytes positive for intracellular IFN-gamma and IL-4 was observed following primary infection with either virus. In contrast, lymphocytes positive for intracellular IL-2 were reduced. Following SIVmacJ5 challenge of SIVmacC8-infected vaccinees, no evidence of detectable superinfection was obtained. Rechallenge of vaccinees did not alter the frequency of activated peripheral T-lymphocytes, perturb cytokine profiles, or generate an anamnestic antibody response. These data do not support the hypothesis that protection conferred by live attenuated SIV is mediated by the induction of vigorous T-cell responses upon rechallenge.