Lv4, an activity that restricts nuclear entry of SIVMAC/SIVSM in human blood cells

SIVSM is a lentivirus endemic to the West African sooty mangabey (Cercocebus atys). HIV-2 and SIVMAC are zoonoses that resulted from SIVSM transmission to humans and Asian rhesus macaques (Macaca mulatto), respectively. Human leukemia cell lines, human peripheral blood mononuclear cells and CD4+ T cells, were 4 to 50-fold less permissive for SIVMAC and SIVSM than for HIV-1. In contrast, SIVMAC transduction of human adherent cell lines was equivalent to that of HIV-1. Consistent with adaptation to human cells, HIV-2 was not restricted as potently as was SIVMAC. SIVMAC transduction of human blood cells was rescued up to the level of HIV-1 by As2O3, a compound that increases the infectivity of viruses in the context of TRIM5-mediated restriction. Nonetheless, efficient knockdown of TRIM5 or cyclophilin A, a cytoplasmic factor that sometimes regulates TRIM5 restriction activity, did not rescue SIVMAC tranduction of these cells. Substitution of HIV-1 CA with the CA from SIVMAC rendered HIV-1 poorly infectious for Jurkat T cells. The block occurred after completion of reverse transcription and the formation of 2-LTR circles, but before establishment of the provirus. Heterokaryons resulting from fusion of permissive with restrictive cells exhibited the restrictive phenotype, indicating that SIV transduction of human blood cells is inefficient due to a dominant-acting restriction factor. These results demonstrate that the nucleus of human blood cells possesses a TRIM5-like restriction factor specific for the SIVMAC/SIVSM capsid and that, by extension, cross-species transmission of SIVSM to human cells necessitated adaptation of HIV-2 to this restriction factor

Substance misuse in personality disorder and schizophrenia : findings and clinical implications from a high secure hospital

Purpose Substance misuse (SMU) is widely prevalent in mentally disordered offenders and is linked with violence and offending behaviour. There is however, a scarcity of literature dedicated to investigating SMU and its clinical correlates in relation to patients detained within high secure hospital settings. The purpose of this paper is to investigate the extent and severity of SMU and corresponding treatment needs in patients with a primary diagnosis of personality disorder (PD) in comparison with mental illness (MI) in a high secure hospital. Design/methodology/approach The responsible clinicians of all patients (n=240) detained in a high secure hospital were asked to record information using a SMU screening questionnaire over a ten-month period. Details requested included substance type, history of past use and assessment and treatment needs. Data were recorded and then analysed: descriptive statistics were conducted to report historical use of substances, cross tabulations and χ2 analysis explored the relationship between SMU and treatment status and diagnosis and offending behaviour and a means comparison analysis was employed to explore length of stay and treatment of SMU. Findings A total of 230 questionnaires were returned (95 per cent of the patient population). A history of SMU was reported in 88.6 per cent of the sample, with alcohol and cannabis misuse being the most prevalent. At least one substance had been abused by 74.3 per cent of the sample. In two-thirds of the sample, SMU was linked with the onset of mental health problems and symptom exacerbation, including violence. Interestingly, patients with a diagnosis of MI as compared with PD were more likely to have used substances (93.3 per cent compared to 81.9 per cent) and were more likely to need treatment for SMU (64.3 per cent compared to 36.8 per cent). In those with an MI diagnosis, SMU was more likely to be linked with violence and index offence (74.3 per cent compared to 59.0 per cent). Practical implications SMU is significantly prevalent in high risk mentally disordered offenders and linked to onset of mental health problems and offending. Patients with schizophrenia have a higher prevalence of SMU than PD and are likely to be more in need of treatment. Violence and offending are more likely to be related to SMU in schizophrenia than in PD. Originality/value This study substantiates existing evidence that SMU contributes to mental health problems and criminogenic behaviour. Furthermore, the study reports new findings that characterize differences of the relationship of SMU to offending in schizophrenia and PD in forensic psychiatric patients presenting to a high secure hospital. </jats:sec