Infecção & Imunidade

Interesse da Investigação

Infections & Immunity

Membros do Grupo

Projecto de Investigação

The potential and application of virus host evasion genes that modify apoptosis and cytokine responses.

The aim is to identify and exploit viral modifiers of apoptosis and cytokine responses (particularly TNFRs) as a potential source of novel health care pharmaceuticals for manipulation of immune responses and treatment of certain diseases. Such virus genes will be identified by nucleotide sequence and functional analysis of cloned viral ORFs and cDNA libraries of three large DNA viruses (African swine fever (ASFV), Ectromelia virus (EV) and Mouse herpes virus (MHV 68)). As a direct approach towards identifying novel virus evasion genes which do not have homologies in the data base, the genes of these three viruses will be systematically screened in functional assays for their impact on apoptosis and cytokine responses. To date, we have identified three novel viral genes inhibiting interferon responses, one gene inducing cell cycle arrest/apoptosis, and one gene inhibiting some, but not all, toll receptor-like signaling pathways. The construction of mice transgenic for selected virus “evasion” genes is now well underway, and will provide a novel approach to explore the mechanism and exploitation of these genes. One particularly interesting transgenic mouse has a defect in T cell development and lymphoid homeostasis, and will provide a novel system to explore basic mechanisms operating in the development of the lymphoid system.

Funding

POCTI/MGI/45100/2002
Viral modulation of cell division, apoptosis and interferon responses.

MGI/36403/99
The potential and application of virus host evasion genes that modify apoptosis and cytokine responses.

EU QLK3 – 2000 – 00362
The potential and application of virus host evasion genes that modify apoptosis and cytokine responses.

Projecto de Investigação

Control of human, bovine and porcine cysticercosis through vaccination and improved diagnosis.

The zoonotic tapeworm Taenia solium, causal agent of life threatening human neurocysticercosis, constitutes an increasingly major health risk. The adult, or tapeworm stage, lives in the intestine of man, whilst the intermediate metacestode stage, responsible for cysticercosis, may occur both on pig and man. The related parasite, Taenia saginata, similarly infects man as an intestinal tapeworm but passes its metacestode stage only in cattle. Rural transmission is mediated by poor sanitation and uncontrolled pig and cow management practices, and so the prevalence of these parasites is an objective indicator of rural poverty. Recently, population movement linked to close human/pig and cow contact in the rural-urban interface has exacerbated the problem. Control through improved sanitation is a major, long-term and expensive goal. This project focuses on the shorter-term, more cost-effective strategies of improving pig and cow management, including village pig vaccination (transmission control) and the development of sensitive and specific diagnostic assays to detect parasites and anti-parasite antibodies; the latter based on synthetic peptides, recombinant reagents and PCR, not parasite material. New diagnostic assays will improve hospital patient monitoring/treatment and man/pig screening and hence epidemiological knowledge. To date, we have succeeded in developing the following diagnostic tests: 1) PCR tests for the differential diagnosis of cestode parasites (Taenia solium, Taenia saginata and E chinococcus); 2) Synthetic peptide based assays to detect antibodies to Taenia parasites and 3) An ELISA assay which detects secreted metacestode antigens and thus viable metacestode parasites in pigs, cattle and man. These are all now being applied in endemic areas, principally Mexico, Peru, Bolivía and Venezuela, and, on occasions, clinical material in Spain. Finally, we have developed a potential vaccine for bovine cysticercosis, based on a recombinant oncospheral surface and secreted molecule which, interesting is functionally, an adhesion molecule, possibly facilitating tissue invasion by the parasite in the intermediatehost.

Colaboradores

Universidad Peruana Cayetano Heredia, Lima, Peru).
Dr. H. Garcia

Instituto de Salud Carlos III, Centro Nacional de Microbiologia, Madrid, Spain
Dr. T. Garate

University of Edinburgh, Department of Tropical Animal Health, Centre for Tropical Veterinary Medicine, Scotland
Dr. L. Harrison

Universidad de Carabobo, Venezuela
Dr. M. Cortez

Universidad Nacional Autonoma de Mexico, Institute de Investigaciones Biomedicas, Mexico
Dr. E. Sciutto

Projecto de Investigação

Control of African swine fever (ASF) through improved diagnosis

African swine fever is one of the most important diseases of pigs. Its control relies solely on efficient diagnosis and application of strict sanitary measures. Vaccine has never been obtained. ASFV infects domestic pigs and Ornithodorus sp. ticks (shown as vectors in Iberian Peninsula before the disease was eradicated). Danger of ASF re-emergence and/or new introduction is a major concern for EU, due to lacking knowledge on mechanisms of viral persistence in the pig and in ticks and because several European countries have close contacts with African countries where the disease is nowadays devastating. The rational of this project is to improve diagnostic methods to enable rapid implementation of prophylatic measures. Our previous work has identified the 12 principle serological determinants of ASFV and the principal aim of this project is to express these viral proteins and assess their potential value as serological diagnostic probes using sera from infected pigs previously obtained. To date, the 12 viral genes have been subcloned into the expression vector and their purification is underway for testing as reliable diagnostic tools.

Funding

EU QLK2 – CT – 2001 – 02216
African swine fever (ASF): improved diagnostic methods and understanding of virus-host epidemiology and virus-host interaction.

Colaboradores

Laboratório de Doenças Infecciosas, Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa
Alexandre Leitão

Publicações

Please consult the respective CV (2004).