TRIM5␣ is a potent barrier to cross-species retroviral transmission, and TRIM5␣s from different species have divergent antiretroviral specificities. Multiple TRIM5 alleles circulate within rhesus macaque populations. Here we show that they too have different antiretroviral specificities, highlighting how TRIM5 genotypes contribute to protection in an individual or a population.TRIM5␣ is an important mediator of antiretroviral innate immunity in mammals and represents a significant barrier to zoonotic transmission. It blocks retroviral infection in a species-specific manner; for example, human immunodeficiency virus type 1 (HIV-1) is restricted by Old World monkey TRIM5␣ but is not significantly restricted by human TRIM5␣ (12,26,31). TRIM5␣ consists of RING, B-box 2, and coiledcoil domains (RBCC), comprising a tripartite motif, as well as a C-terminal B30.2 domain, which determines antiviral specificity, and appears to interact directly with the incoming viral capsid (27). Recently, multiple TRIM5 alleles have been identified in an Old World monkey, the rhesus macaque (Macaca mulatta) (17). These alleles have surprisingly divergent B30.2 domains and are maintained at high frequencies in macaque populations. Because variation in the sequence of the B30.2 domain can have such profound effects on the antiretroviral specificity of TRIM5␣, these divergent macaque B30.2 domains have likely been selected to interact with different viral capsids. Remarkably, one of the TRIM5 alleles, Mamu-7, encodes a TRIM5-cyclophilin A (CypA) fusion protein with a different spectrum of antiretroviral activity to TRIM5␣ (4, 13, 18, 29, 30). In Mamu-7/TRIMCyp, exon 6 is joined to a downstream CypA cDNA sequence, leaving a vestigial B30.2 domain in the genome (Fig. 1A). Here we demonstrate the differential restriction of HIV-2 by rhesus TRIM5 alleles and map the determinant of restriction to a polymorphism in the B30.2 V1 region. Furthermore, we show that the different TRIM5 alleles have dominant negative properties against each other when exogenously expressed.To further characterize the degree of polymorphism in rhesus macaques, we sequenced TRIM5 exon 8 from DNA purified from 31 Indian and 38 Chinese Macaca mulatta monkeys from the Biomedical Primate Research Centre breeding colony in Rijswijk, The Netherlands (30). We identified the TRIM5 alleles 30). Predicted B30.2 domain amino acid sequences are shown in Fig. 1B. We also identified a mutation, G402D, in one animal. We are unsure whether this represents a mutation or a genuine polymorphism but have included it in our analyses. In order to explore the antiretroviral specificities of the various B30.2 domains, we generated a murine leukemia virus (MLV)-based vector (32) that expresses TRIM5␣ Mamu-1, driven by an internal cytomegalovirus promoter, with a silent SalI site at the V-301 and D-302 codons, facilitating the insertion of the entire exon 8 sequences from at this site. We then transduced CRFK cells with vectors encoding the different B30.2 domains appended to the hemagglutinin...
This review focused on GBC surgery. Peritoneal carcinomatosis is common. In carefully selected patients, the incorporation of peritoneal disease in cytoreductive surgery and intraperitoneal chemotherapy will inhibit a vehicle for dissemination, eliminate future relapse sites and improve survival. Areas for consideration include universally standardised protocols, clear management guidelines for each stage, effective re-resection timings with guidance on where or how to identify additional disease.
HIV/AIDS continues to spread globally and remains a worldwide pandemic affecting about 40 million people. The prevention of infection remains paramount to vaccine studies. Although the best immune correlates for an efficacious HIV vaccine have not yet been discovered, progress has been made toward developing a vaccine. The identification of an effective antibody-binding site, targeted by a functional neutralizing antibody, and findings confirming that the Gag-specific responses are effective in protecting against disease progression are major advances in this field. This review highlights immunology-based developments in vaccine research and viral and host cell properties that could be employed to curb the spread of HIV.
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