Wrapping up the bad news: HIV assembly and release.

The late Nobel Laureate Sir Peter Medawar once memorably described viruses as 'bad news wrapped in protein'. Virus assembly in HIV is a remarkably well coordinated process in which the virus achieves extracellular budding using primarily intracellular budding machinery and also the unusual phenomenon of export from the cell of an RNA. Recruitment of the ESCRT system by HIV is one of the best documented examples of the comprehensive way in which a virus hijacks a normal cellular process. This review is a summary of our current understanding of the budding process of HIV, from genomic RNA capture through budding and on to viral maturation, but centering on the proteins of the ESCRT pathway and highlighting some recent advances in our understanding of the cellular components involved and the complex interplay between the Gag protein and the genomic RNA.

Emergence of host-adapted Salmonella Enteritidis through rapid evolution in an immunocompromised host.

Host adaptation is a key factor contributing to the emergence of new bacterial, viral and parasitic pathogens. Many pathogens are considered promiscuous because they cause disease across a range of host species, while others are host-adapted, infecting particular hosts1. Host adaptation can potentially progress to host restriction where the pathogen is strictly limited to a single host species and is frequently associated with more severe symptoms. Host-adapted and host-restricted bacterial clades evolve from within a broader host-promiscuous species and sometimes target different niches within their specialist hosts, such as adapting from a mucosal to a systemic lifestyle. Genome degradation, marked by gene inactivation and deletion, is a key feature of host adaptation, although the triggers initiating genome degradation are not well understood. Here, we show that a chronic systemic non-typhoidal Salmonella infection in an immunocompromised human patient resulted in genome degradation targeting genes that are expendable for a systemic lifestyle. We present a genome-based investigation of a recurrent blood-borne Salmonella enterica serotype Enteritidis (S. Enteritidis) infection covering 15 years in an interleukin (IL)-12 ß-1 receptor-deficient individual that developed into an asymptomatic chronic infection. The infecting S. Enteritidis harbored a mutation in the mismatch repair gene mutS that accelerated the genomic mutation rate. Phylogenetic analysis and phenotyping of multiple patient isolates provides evidence for a remarkable level of within-host evolution that parallels genome changes present in successful host-restricted bacterial pathogens but never before observed on this timescale. Our analysis identifies common pathways of host adaptation and demonstrates the role that immunocompromised individuals can play in this process.

Does venesection reduce HIV viral load in patients with hereditary haemochromatosis?

It is recognized that iron overload is associated with excess mortality in HIV/AIDS, and that this may be due to iron acting as an HIV-1 transcriptional activator. In vitro evidence using iron chelators suggests that therapeutic iron depletion may be beneficial in HIV-1 infection. We describe the clinical course of a Caucasian man with hereditary haemochromatosis and HIV infection where a significant drop in HIV viral load accompanied venesection over an 18-month period in the absence of HAART. We propose that further research should be undertaken to explore the relationship between HIV viral load and serum iron markers in hereditary haemochromatosis, with a view to evaluating the therapeutic benefit of venesection on HIV viral load in this setting.

Herpes simplex I encephalitis presenting as a brain haemorrhage with normal cerebrospinal fluid analysis: a case report.

INTRODUCTION: Herpes simplex encephalitis is a potentially lethal infection that should be recognised as soon as possible. The combination of clinical history and examination, brain computed tomography or magnetic resonance imaging and lumbar puncture has been used to establish a diagnosis. CASE PRESENTATION: We present a patient who had a suggestive history but a totally normal lumbar puncture and only evidence of intracerebral haemorrhage in the brain magnetic resonance imaging. Diagnosis was made by using the cerebrospinal fluid polymerase chain reaction for herpes simplex virus. CONCLUSION: Herpes simplex encephalitis is being increasingly diagnosed with the availability of new diagnostic techniques. Herpes simplex encephalitis can present with the combination of haemorrhage and normal cerebrospinal fluid. Awareness of this common but, if left untreated, devastating condition should increase.

Chromatin, gene silencing and HIV latency.

One of the cellular defenses against virus infection is the silencing of viral gene expression. There is evidence that at least two gene-silencing mechanisms are used against the human immuno-deficiency virus (HIV). Paradoxically, this cellular defense mechanism contributes to viral latency and persistence, and we review here the relationship of viral latency to gene-silencing mechanisms.