The Structural Interface between HIV-1 Vif and Human APOBEC3H.

Human APOBEC3H (A3H) is a cytidine deaminase that inhibits HIV-1 replication. To evade this restriction, the HIV-1 Vif protein binds A3H and mediates its proteasomal degradation. To date, little information on the Vif-A3H interface has been available.

Functional characterization of Vif proteins from HIV-1 infected patients with different APOBEC3G haplotypes.

Objective: The human cytidine deaminase APOBEC3G (A3G) potently restricts HIV-1 but the virus, in turn, expresses a Vif protein which degrades A3G. A natural A3G-H186R variant, common in African populations, has been associated with a more rapid AIDS disease progression, but the underlying mechanism remains unknown. We hypothesized that differences in HIV-1 Vif activity towards A3G wild type and A3G-H186R contribute to the distinct clinical AIDS manifestation.

Identification of the HIV-1 Vif and Human APOBEC3G Protein Interface.

Human cells express natural antiviral proteins, such as APOBEC3G (A3G), that potently restrict HIV replication. As a counter-defense, HIV encodes the accessory protein Vif, which binds A3G and mediates its proteasomal degradation. Our structural knowledge on how Vif and A3G interact is limited, because a co-structure is not available.

Origin of the HIV-1 group O epidemic in western lowland gorillas.

HIV-1, the cause of AIDS, is composed of four phylogenetic lineages, groups M, N, O, and P, each of which resulted from an independent cross-species transmission event of simian immunodeficiency viruses (SIVs) infecting African apes. Although groups M and N have been traced to geographically distinct chimpanzee communities in southern Cameroon, the reservoirs of groups O and P remain unknown. Here, we screened fecal samples from western lowland (n = 2,611), eastern lowland (n = 103), and mountain (n = 218) gorillas for gorilla SIV (SIVgor) antibodies and nucleic acids.

High prevalence of vitamin D deficiency and insufficiency in patients with manifest Huntington disease: An explorative study.

Vitamin D deficiency and insufficiency are common in older institutionalized people and known to be associated with muscle weakness, impaired balance and increased fall risk. Falls and balance problems are common in people with Huntington disease (HD). Despite this, the prevalence of vitamin D deficiency in patients with manifest HD has never been investigated.

Direct non-productive HIV-1 infection in a T-cell line is driven by cellular activation state and NFκB.

Background: Molecular latency allows HIV-1 to persist in resting memory CD4+ T-cells as transcriptionally silent provirus integrated into host chromosomal DNA. Multiple transcriptional regulatory mechanisms for HIV-1 latency have been described in the context of progressive epigenetic silencing and maintenance. However, our understanding of the determinants critical for the establishment of latency in newly infected cells is limited.

HIV-1 Vif adaptation to human APOBEC3H haplotypes.

Several human APOBEC3 deaminases can inhibit HIV-1 replication in vitro. HIV-1 Vif counteracts this restriction by targeting APOBEC3 for proteasomal degradation. Human APOBEC3H (A3H) is highly polymorphic, with natural variants differing considerably in anti-HIV-1 activity in vitro.

APOBEC3G polymorphism as a selective barrier to cross-species transmission and emergence of pathogenic SIV and AIDS in a primate host.

Cellular restriction factors, which render cells intrinsically resistant to viruses, potentially impose genetic barriers to cross-species transmission and emergence of viral pathogens in nature. One such factor is APOBEC3G. To overcome APOBEC3G-mediated restriction, many lentiviruses encode Vif, a protein that targets APOBEC3G for degradation.

Vif proteins from diverse primate lentiviral lineages use the same binding site in APOBEC3G.

APOBEC3G (A3G) is a cytidine deaminase that restricts human immunodeficiency virus type 1 (HIV-1) and other lentiviruses. Most of these viruses encode a Vif protein that directly binds A3G and leads to its proteasomal degradation. Both Vif proteins of HIV-1 and African green monkey simian immunodeficiency virus (SIVagm) bind residue 128 of A3G.

The resistance of human APOBEC3H to HIV-1 NL4-3 molecular clone is determined by a single amino acid in Vif.

Some human APOBEC3 cytidine deaminases have antiviral activity against HIV-1 and other retroviruses. The single deaminase domain APOBEC3H (A3H) enzyme is highly polymorphic and multiple A3H haplotypes have been identified. A3H haplotype II (A3H-hapII) possesses the strongest activity against HIV-1.

A doubly fluorescent HIV-1 reporter shows that the majority of integrated HIV-1 is latent shortly after infection.

HIV-1 latency poses a major barrier to viral eradication. Canonically, latency is thought to arise from progressive epigenetic silencing of active infections. However, little is known about when and how long terminal repeat (LTR)-silent infections arise since the majority of the current latency models cannot differentiate between initial (LTR-silent) and secondary (progressive silencing) latency.

APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 restrict human T-lymphotropic virus type 1.

The human APOBEC3 family consists of seven cytidine deaminases (A3A to A3H), some of which display potent antiretroviral activity against HIV-1 and other retroviruses. Studies that analyzed the effect of A3G on human T-lymphotropic virus type 1 (HTLV-1) infectivity resulted in conflicting findings, and our knowledge of HTLV-1 restriction by other A3 proteins remains limited. Since HTLV-1, much like HIV, targets CD4(+) T cells, we hypothesized that A3 proteins other than A3G restrict HTLV-1.

The activity spectrum of Vif from multiple HIV-1 subtypes against APOBEC3G, APOBEC3F, and APOBEC3H.

The APOBEC3 family comprises seven cytidine deaminases (APOBEC3A [A3A] to A3H), which are expressed to various degrees in HIV-1 susceptible cells. The HIV-1 Vif protein counteracts APOBEC3 restriction by mediating its degradation by the proteasome. We hypothesized that Vif proteins from various HIV-1 subtypes differ in their abilities to counteract different APOBEC3 proteins.

Identification and functional analysis of a second RBF-2 binding site within the HIV-1 promoter.

Transcription from the HIV-1 long terminal repeat (LTR) is mediated by numerous host transcription factors. In this study we characterized an E-box motif (RBE1) within the core promoter that was previously implicated in both transcriptional activation and repression. We show that RBE1 is a binding site for the RBF-2 transcription factor complex (USF1, USF2, and TFII-I), previously shown to bind an upstream viral element, RBE3.

Moderate influence of human APOBEC3F on HIV-1 replication in primary lymphocytes.

Multiple APOBEC3 proteins are expressed in HIV-1 target cells, but their individual contributions to viral suppression when expressed at endogenous levels remain largely unknown. We used an HIV NL4-3 mutant that selectively counteracts APOBEC3G (A3G) but not APOBEC3F (A3F) to dissect the relative contribution of A3F to the inhibition of HIV-1 replication in primary human lymphocytes (peripheral blood mononuclear cells [PBMCs]). This HIV Vif mutant replicated similarly to wild-type virus in PBMCs, suggesting that the effect of A3F on HIV restriction in these cells is limited.

The localization of APOBEC3H variants in HIV-1 virions determines their antiviral activity.

Several members of the human APOBEC3 family of cytidine deaminases can potently restrict retroviruses such as HIV-1. The single-domain APOBEC3H (A3H) is encoded by four haplotypes, of which only A3H haplotype II-RDD (hapII-RDD) restricts HIV-1 efficiently. The goal of this study was to elucidate the mechanisms underlying the differences in antiviral activity among A3H haplotypes.

Social well-being and its measurement in the nursing home, the SWON-scale.

Aims And Objectives: The aim of this study was to develop an observational scale to measure the social well-being of nursing home residents, by assessing not only the social behaviour of the resident towards others, but also the behaviour of others towards the resident.

Background: Traditionally, aspects of the social well-being of nursing home residents are assessed according to the social activities and interactions where they engage. Although these are important indicators of social well-being, other important indicators may include the positive social behaviour of others towards the resident (e.

Polymorphisms and splice variants influence the antiretroviral activity of human APOBEC3H.

Human APOBEC3H belongs to the APOBEC3 family of cytidine deaminases that potently inhibit exogenous and endogenous retroviruses. The impact of single nucleotide polymorphisms (SNP) and alternative splicing on the antiretroviral activity of human APOBEC3H is currently unknown. In this study, we show that APOBEC3H transcripts derived from human peripheral blood mononuclear cells are polymorphic in sequence and subject to alternative splicing.

Destabilization of the TAR hairpin affects the structure and function of the HIV-1 leader RNA.

The TAR hairpin of the human immunodeficiency virus type 1 (HIV-1) RNA genome is essential for virus replication. TAR forms the binding site for the transcriptional trans-activator protein Tat and multiple additional TAR functions have been proposed. We previously constructed an HIV-1 variant in which the TAR-Tat transcription control mechanism is replaced by the components of the Tet-ON regulatory system.

Optimization of the doxycycline-dependent simian immunodeficiency virus through in vitro evolution.

Background: Vaccination of macaques with live attenuated simian immunodeficiency virus (SIV) provides significant protection against the wild-type virus. The use of a live attenuated human immunodeficiency virus (HIV) as AIDS vaccine in humans is however considered unsafe because of the risk that the attenuated virus may accumulate genetic changes during persistence and evolve to a pathogenic variant. We earlier presented a conditionally live HIV-1 variant that replicates exclusively in the presence of doxycycline (dox).

A revised Index for Social Engagement for long-term care.

The objective of this study was to improve validity and reliability estimates of the Index for Social Engagement (ISE) for long-term care. After exploring content validity and internal consistency in Dutch and Canadian data, two ISE items were dropped, and two new items were added. Reliability of this Revised ISE (RISE) was tested in 189 nursing home residents.

Circularization of the HIV-1 RNA genome.

Genomic RNA circularization has been proposed for several RNA viruses. In this study, we examined if the 5' and 3' ends of the 9-kb HIV-1 RNA genome can interact. In vitro assays demonstrated a specific interaction between transcripts encompassing the 5' and 3' terminal 1 kb, suggesting that the HIV-1 RNA genome can circularize.

Construction of a doxycycline-dependent simian immunodeficiency virus reveals a nontranscriptional function of tat in viral replication.

In the quest for an effective vaccine against human immunodeficiency virus (HIV), live attenuated virus vaccines have proven to be very effective in the experimental model system of simian immunodeficiency virus (SIV) in macaques. However, live attenuated HIV vaccines are considered unsafe for use in humans because the attenuated virus may accumulate genetic changes during persistence and evolve to a pathogenic variant. As an alternative approach, we earlier presented a conditionally live HIV-1 variant that replicates exclusively in the presence of doxycycline (DOX).

Measurement of overall quality of life in nursing homes through self-report: the role of cognitive impairment.

Measuring quality of life is a necessity for adequate interventions. This paper concerns the usefulness of six self-report measures for overall quality of life for nursing home residents with various levels of cognitive impairment. It was investigated which proportion of residents from four cognition groups could complete a scale, and internal consistency and construct validity of the scales were studied.

Starting artificial nutrition and hydration in patients with dementia in The Netherlands: frequencies, patient characteristics and decision-making process.

Background And Aims: In many patients with dementia, the oral intake of fluids and nutrients becomes insufficient and a decision has to be made whether to start artificial nutrition or hydration (ANH). This study examines the incidence of ANH in nursing-home patients with dementia in The Netherlands, the methods of administration used, patient characteristics, and the characteristics of the ANH decision- making process.

Methods: In June 2001, a postal questionnaire was sent to all nursing-home physicians (NHPs) (n=1054) in The Netherlands.