؉ T lymphocytes. Considering that the HIV-1 life cycle is tightly regulated by the T cell signaling machinery, the priming for activation of a major viral reservoir represents a means by which this retrovirus can create an ideal cellular microenvironment for its propagation and maintenance.

We have examined the molecular basis for the selective incorporation of the adhesion molecule ICAM-1 within human immunodeficiency virus type 1 (HIV-1). The process of ICAM-1 incorporation was investigated by using different ICAM-1 constructs in combination with virus capture and immunoprecipitation studies, Western blot and confocal microscopy analyses, and infectivity assays. Experiments conducted with viruses bearing a truncated version of ICAM-1 revealed that the cytoplasmic domain of ICAM-1 governs insertion of this adhesion molecule into HIV-1. Further experiments suggested that there is an association between ICAM-1 and the virus-encoded Pr55Gag polyprotein. This study represents the first demonstration that structural Gag polyproteins play a key role in the uptake of a host-derived cell surface by the virus entity. Taken together, our results indicate that interactions between viral and cellular proteins are responsible for the selective uptake of host ICAM-1 by HIV-1. This observation describes a new strategy by which HIV-1 can modulate its replicative cycle, considering that insertion of ICAM-1 within nascent virions has been shown to increase virus infectivity.

Previous works have indicated that incorporation of surface glycoprotein into retroviruses such as the human immunodeficiency virus type 1 (HIV-1) is not a highly specific process because several cellular glycoproteins can be inserted within the mature viral particle. The mechanism(s) that govern the acquisition of such host constituents have remained so far elusive. In this study, we have investigated the role played by the viral envelope (Env) of HIV-1 in the acquisition of host intercellular adhesion molecule type I (ICAM-1). ICAM-1 proteins were still present on viruses carrying much lower levels of gp120/gp41 due to a mutation in the matrix (MA) domain or on Env-deficient viruses when produced in immortalized and primary human cell lines. Interestingly, infectivity of an HIV-1 MA mutant that carry a suboptimal amount of Env proteins was restored to a certain degree by the presence of ICAM-1 when infection was performed in cells expressing an activated form of its natural counter-ligand, LFA-1.

HLA-DR is a host-derived protein present at the surface of HIV-1. To clarify the mechanism through which this molecule is inserted within viruses, we monitored whether the incorporation process might be influenced by the level of virus-encoded envelope (Env) glycoproteins. Wild-type virions and viruses either lacking or bearing lower levels of Env were produced in different cell types. Results from a virus capture test indicate that HLA-DR is efficiently incorporated and at comparable levels in the tested virus preparations. Therefore, Env does not play an active role in the acquisition of host HLA-DR by emerging HIV-1 particles.

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Benign recurrent intrahepatic cholestasis is a rare clinical entity that is caused by mutations in the canalicular transport genes. The present report describes two individuals from the same family whose symptoms were typical of the clinical characteristics of type 2 benign recurrent intrahepatic cholestasis. Sequencing of the ABCB11 gene revealed two previously unreported mutations that predict the absence of expression of the protein. The clinical presentation of the current cases are discussed, as are the differential diagnosis and genetic characteristics of the hereditary cholestatic disorders, overemphasizing the possibility of making a definite genetic diagnosis.

In their comment on our article describing the calculation of a risk exposure score [1], Gerberry and Blower [2] argue that the score only applies retrospectively, is unlikely to be calculable in the real world, and has so much uncertainty that it is unhelpful.We disagree, first, like all studies of risk, the score is based on past studies, but the calculation can be applied both to recent behaviour and to explore how risk could be modified. This is the typical basis of risk counselling. Second, in our HIV clinics, many people in discordant partnerships do know the viral load and HIV stage of their partner. Third, the way that the variation based on uncertainty is presented by Gerberry and Blower [2] is misleading: taking the upper bounds of the 95% confidence interval (CI) for two parameters and using them together gives an upper 99.875% confidence bound, and similarly for the lower bounds. For three parameters, the bounds get even wider. Thus, 'using the limits of the 95% CIs for each of the included risk factors' creates extreme ranges. In our article, we presented 95%

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