Matthew Collin

HIV-1 induces tumour necrosis factor and IL-1 gene expression in primary human macrophages independent of productive infection.

Cylokines such as tumour necrosis factor‐alpha (TNF‐a) and IL‐Iβ may play a role in immunopalhogcncsis of AIDS, We studied early effects (05‐48 h) of monocytotropic (ADA) or tymp ho tropic (1MB) strains of HIV‐1 on TNF‐α and IL‐1β mRNA expression in primary human macrophages by a semi‐quantitative reverse transcriptase‐polymcrase chain reaction (RT‐PCR) assay. Three‐day‐old monocyte‐derived macrophages were exposed either to tissue culture supernatants containing virus (at multiplicity of infection (m.o.i.) of 005) or to control supernatants frceofvirionsandgpI20. ADA strain, but not IIIB. replicated in primary tissue culture‐differentiated macrophages (TCDM). Soluble CD4 (sC D4) was used to inhibit binding of both strains to macrophages. We found that TNF‐arand IL‐lβ gene expression was induced by both strains 0‐5‐3 hafter addition of virus, and that enhanced expression of both cytokines was inhibited by sCD4. We conclude that C D4‐dependcnl binding lo ihc cell surface is sufficient to enhance TNI′‐α and ll.‐lβ mRNA. whereas productive viral replication in primary human macrophages is not required. Therefore, similar pathways regulate gene expression of TNF‐a and IL‐Iβ by macrophages during initial infection by HIV‐1 in vitro.

Definition of the range and distribution of human immunodeficiency virus macrophage tropism using PCR-based infectivity measurements

The tropism of human immunodeficiency virus (HIV) for macrophages (m phi) is a well recognized phenomenon, but the range and distribution of m phi-tropic phenotypes have not been defined by quantitative means. This study uses a PCR-based infectivity assay to derive an index of m phi tropism for several common strains of HIV. The results show that m phi tropism varies over about six orders of magnitude and that the most m phi-tropic strains have a higher infectivity for m phi than for peripheral blood lymphocytes. Strains were distributed throughout this range, suggesting that m phi tropism is a continuously variable phenotypic property. Although the degree of tropism was strongly influenced by the mode of isolation and propagation of virus strains, there was no evidence for the existence of distinct m phi-tropic or non-m phi-tropic phenotypes. Finally, the tropism of two selected strains was found to be determined by an early step in replication, probably virus entry.

Development of techniques to analyse the formation of HIV provirus in primary human macrophages

The formation of provirus is an important early event in the life cycle of a retrovirus. We describe a system using PCR for the analysis of this process in primary human macrophages infected in vitro with HIV. We show that products of the first template switch can be detected within 8 h after infection at low multiplicity. The methods described provide a rapid assay of infection with HIV and can be applied in the investigation of a number of aspects of HIV replication in macrophages.

PCR analysis of HIV1 infection of macrophages: virus entry is CD4-dependent.

Amplification of early reverse transcripts by the polymerase chain reaction has been used to measure HIV1 entry into H9 cells and primary macrophages. With a single-step method of DNA preparation, we performed time course experiments to follow the appearance of long terminal repeat DNA. In both cell types, the formation of DNA was completely inhibited by anti-CD4 antibody, confirming the requirement of CD4 for virus binding and entry, and demonstrating that there were no CD4-independent routes of infection. In agreement with previous infectivity studies, sCD4 inhibited the entry of IIIB into H9, but only partially blocked Ba-L into macrophage when used at a comparable dose.

The Impact of Anti-Money Laundering Regulation on Payment Flows: Evidence from SWIFT Data

Regulatory pressure on international banks to fight money laundering (ML) and terrorist financing (TF) increased substantially in the past decade. At the same time there has been a rise in the number of complaints of banks denying transactions or closing the accounts of customers either based in high risk countries or attempting to send money there, a process known as de-risking. In this paper, we investigate the impact of an increase in regulatory risk, driven by the inclusion of countries on an internationally-recognized list of high risk jurisdictions, on subsequent cross-border payments. We find countries that have been added to a high risk greylist face up to a 10 percent decline in the number of cross border payments received from other jurisdictions, but no change in the number sent. We also find that a greylisted country is more likely to see a decline in payments from other countries with weak AML/CFT institutions. We find limited evidence that these effects manifest in cross border trade or other flows. Given that countries that are placed on these lists tend to be poorer on average, these impacts are likely to be more strongly felt in developing countries.