Host cell species-specific effect of cyclosporine A on simian immunodeficiency virus replication

<p>Abstract</p> <p>Background</p> <p>An understanding of host cell factors that affect viral replication contributes to elucidation of the mechanism for determination of viral tropism. Cyclophilin A (CypA), a peptidyl-prolyl <it>cis-trans </it>isomerase (PPIase), is a host factor essential for efficient replication of human immunodeficiency virus type 1 (HIV-1) in human cells. However, the role of cyclophilins in simian immunodeficiency virus (SIV) replication has not been determined. In the present study, we examined the effect of cyclosporine A (CsA), a PPIase inhibitor, on SIV replication.</p> <p>Results</p> <p>SIV replication in human CEM-SS T cells was not inhibited but rather enhanced by treatment with CsA, which inhibited HIV-1 replication. CsA treatment of target human cells enhanced an early step of SIV replication. CypA overexpression enhanced the early phase of HIV-1 but not SIV replication, while CypA knock-down resulted in suppression of HIV-1 but not SIV replication in CEM-SS cells, partially explaining different sensitivities of HIV-1 and SIV replication to CsA treatment. In contrast, CsA treatment inhibited SIV replication in macaque T cells; CsA treatment of either virus producer or target cells resulted in suppression of SIV replication. SIV infection was enhanced by CypA overexpression in macaque target cells.</p> <p>Conclusions</p> <p>CsA treatment enhanced SIV replication in human T cells but abrogated SIV replication in macaque T cells, implying a host cell species-specific effect of CsA on SIV replication. Further analyses indicated a positive effect of CypA on SIV infection into macaque but not into human T cells. These results suggest possible contribution of CypA to the determination of SIV tropism.</p

The hippocampal sharp wave–ripple in memory retrieval for immediate use and consolidation

Various cognitive functions have long been known to require the hippocampus. Recently, progress has been made in identifying the hippocampal neural activity patterns that implement these functions. One such pattern is the sharp wave-ripple (SWR), an event associated with highly synchronous neural firing in the hippocampus and modulation of neural activity in distributed brain regions. Hippocampal spiking during SWRs can represent past or potential future experience, and SWR-related interventions can alter subsequent memory performance. These findings and others suggest that SWRs support both memory consolidation and memory retrieval for processes such as decision-making. In addition, studies have identified distinct types of SWR based on representational content, behavioural state and physiological features. These various findings regarding SWRs suggest that different SWR types correspond to different cognitive functions, such as retrieval and consolidation. Here, we introduce another possibility - that a single SWR may support more than one cognitive function. Taking into account classic psychological theories and recent molecular results that suggest that retrieval and consolidation share mechanisms, we propose that the SWR mediates the retrieval of stored representations that can be utilized immediately by downstream circuits in decision-making, planning, recollection and/or imagination while simultaneously initiating memory consolidation processes