U.S. Rajapaksa

HLA-B may be more protective against HIV-1 than HLA-A because it resists negative regulatory factor (Nef) mediated down-regulation.

Human leukocyte antigen HLA-B alleles have better protective activity against HIV-1 than HLA-A alleles, possibly due to differences in HLA-restricted HIV-1-specific CD8+ cytotoxic T lymphocyte (CTL) function, but the mechanism is unknown. HIV-1 negative regulatory factor (Nef) mediates down-regulation of surface expression of class I HLA (HLA-I) and may therefore impair immune recognition by CTL. Because of sequence differences in the cytoplasmic domains, HLA-A and -B are down-regulated by Nef but HLA-C and -E are not affected. However, the latter are expressed at low levels and are not of major importance in the CTL responses to HIV-1. Here, we compared the role of the cytoplasmic domains of HLA-A and -B in Nef-mediated escape from CTL. We found HLA-B cytoplasmic domains were more resistant to Nef-mediated down-regulation than HLA-A cytoplasmic domains and demonstrated that these differences affect CTL recognition of virus-infected cells in vitro. We propose that the relative resistance to Nef-mediated down-regulation by the cytoplasmic domains of HLA-B compared with HLA-A contributes to the better control of HIV-1 infection associated with HLA-B-restricted CTLs.

Molecular diversity of Mycobacterium tuberculosis isolates from patients with pulmonary tuberculosis in Sri Lanka.

The strain diversity of 100 Mycobacterium tuberculosis isolates collected over a period of 18 months from tuberculosis (TB) cases in Sri Lanka was studied by spoligotyping. When compared to the international spoligotyping database, 43 spoligotype patterns were identified, of which 20 were previously described. The majority of isolates (72.45%) were clustered into major genetic group 1, and the most common spoligotype pattern belonged to the Beijing (ST1) strain family. All the Beijing strain isolates belonged to more recently evolved sublineages of M. tuberculosis. The characterization of Sri Lankan M. tuberculosis isolates by spoligotyping shows a heterogeneous pattern. The physical separation from the main Indian peninsula may be responsible for the different patterns observed between the two countries. An in-depth field study is needed to understand the spread and the true epidemiology of this infection.

Microculture for the isolation of Leishmania, modified to increase efficacy: a follow-up to a previous study

In studies on the leishmaniases, the identification of the parasites to species level, by iso-enzyme characterization or by most molecular biological techniques, requires the isolation of the parasites in culture. Novy, McNeal and Nicolle (NNN) and Evan’s modified Tobie’s (EMTb) are two conventional media commonly used for the isolation of Leishmania parasites from blood or tissue samples of patients. Both are biphasic, with a solid agar layer that has to be enriched with blood, and EMTb medium is based on relatively expensive reagents. The preparation of both of these media is laborious and time-consuming, and neither supports the multiplication of all Leishmania parasites from humans (Allahverdiyev et al., 2004; Ihalamulla et al., 2005). A monophasicmicroculture (MCC) method that only uses very small volumes of RPMI 1640 supplemented with 20% foetal calf serum (FCS) has recently been described by Ihalamulla et al. (2005). In the detection of human cutaneous leishmaniasis in Sri Lanka, this method, which involves the sealing with wax of a 1:1 mix of the medium and a sample of saline aspirate from a skin lesion in a microhaematocrit capillary tube, gives higher sensitivity than the culture of similar aspirates in NNN or EMTb medium (Ihalamulla et al., 2005). The possibility that the efficacy of the MCC method could be further improved, in effect by keeping all the parasites that are in the aspirate sample but replacing the saline with more medium, has now been explored.

Sublineages of Beijing Strain of Mycobacterium tuberculosis in Sri Lanka

Strains of the Beijing/W genotype of Mycobacterium tuberculosis have been responsible for large outbreaks of tuberculosis around the world, sometimes involving multi-drug resistance. It has been shown that more recently evolved Beijing sublineages are prone to cause outbreaks. Furthermore Beijing is the single predominant cluster in Sri Lanka. The present study identifies that recently evolved sublineages of Beijing strains are present in the study population. The majority of Beijing isolates (92.85%) were pan-susceptible. However, these findings may have important implications for the control and prevention of tuberculosis in Sri Lanka.

A Comprehensive Analysis of the Impact of HIV on HCV Immune Responses and Its Association with Liver Disease Progression in a Unique Plasma Donor Cohort.

Objective Human Immunodeficiency Virus (HIV) and Hepatitis C virus (HCV) co-infection is recognized as a major cause of morbidity and mortality among HIV-1 infected patients. Our understanding of the impact of HIV infection on HCV specific immune responses and liver disease outcome is limited by the heterogeneous study populations with genetically diverse infecting viruses, varying duration of infection and anti-viral treatment. Methods Viral-specific immune responses in a cohort of 151 HCV mono- and HIV co-infected former plasma donors infected with a narrow source of virus were studied. HCV and HIV specific T cell responses were correlated with clinical data. Results HIV-1 accelerated liver disease progression and decreased HCV specific T cell immunity. The magnitude of HCV specific T cell responses inversely correlated with lower HCV RNA load and reduced liver injury as assessed by non-invasive markers of liver fibrosis. HIV co-infection reduced the frequency of HCV specific CD4+ T cells with no detectable effect on CD8+ T cells or neutralizing antibody levels. Conclusion Our study highlights the impact of HIV co-infection on HCV specific CD4+ T cell responses in a unique cohort of patients for both HCV and HIV and suggests a crucial role for these cells in controlling chronic HCV replication and liver disease progression.