Concerted action on HIV variability

Información del proyecto

Identificador del acuerdo de subvención: MR4*0365

Proyecto cerrado

Fecha de inicio 1 Diciembre 1991

Fecha de finalización 31 Diciembre 1993

Financiado con arreglo a

• Research and development coordination programme (EEC) in the field of medical and health research, 1987-1991

Coste total

Sin datos

Aportación de la UE

Sin datos

Coordinado por

Seminario Romano Ricerche sul Cancro
Italy

Objetivo

The objectives were as follows:
- to characterize different HIV isolates at biological level, mainly focusing on different cellular tropism;
- to verify whether changes in biological features may occur in the same patient during the course of infection;
- to define the genomic regions that determine the different biological phenotypes;
- to isolate and characterize drug-resistant virus strains from patients under anti-viral treatment;
- to map immuno-dominant epitopes on structural and regulatory viral proteins in different isolates;
- to provide a forum for coordination and bridging of the EC activity derived from the CA, i.e. the Centralized Facility (CF) for genetic analyses of HIV strains (sequencing and cloning), and the preparatory activity sponsored by EC funds aimed at collecting HIV-1 strains from different countries for molecular epidemiology and research supportive of the EVA effort.
Human immunodeficiency virus (HIV) exhibits a high degree of genetic polymorphism which results in widespread antigenic variability and in different patterns of virus infection and cytopathogenicity in culture and possibly in vivo. Whether and how these features influence the course of acquired immune deficiency syndrome (AIDS) is basically unknown. It is thus mandatory to elucidate the role played by the viral heterogeneity in determining the course of the disease and its variable pattern.

HIV-1 isolates show variation in syncytium inducing (SI) capacity, replication rate and cell tropism. Emergence of SI variants in an individual usually precede increases in viral load and accelerate CD4 cell decline. The incidence of non SI/SI conversion is rare following AIDS diagnosis. Analysis of a large panel of primary isolates demonstrated that the NSI/SI conversion was often preceded by the acquisition of an additional potential glycosylation site in the V2 domain.

Determinants of monocytotropism were analyzed and revealed restrictions at entry and postentry levels. In the latter case viral entry did not result in establishment of productive infection since only partial proviral deoxyribonucleic acid (DNA) species were synthesized, suggesting an insufficient support of the reverse transcriptase (RT) process from both viral and cellular factors.

Functional impairment of antigen presenting cells due to HIV infection may be the basis for the induction of early T-cell dysfunction in humans. Additional evidence for this was obtained from studies on 3 long term HIV infected health chimpanzees. The incapability of HIV to infect chimpanzee monocytic cells (APC) therefore may be the basis for the absence of induction of systemic immune dysfunction in these animals.

Antigenic variability of the virus, as detected by virus neutralization, may have profound effects on pathogenesis. Even if the immune response is able to efficiently suppress virus replication, emergence of antigenic variant viruses resistant to neutralization by the infected host's own antibodies soon occurs. The ability to produce neutralizing antibodies to several variant viruses seems to be related to a slower pathogenic process. In addition, neutralizing antibodies present in the mother may prevent transmission of HIV-1 to the child. In conclusion, virus heterogeneity may play a fundamental role in the pathogenic process. When virus replication is slower fewer variants are produced. The immune system may be able to better hold in check a relatively limited number of variants slowing down the pathogenic process. In this respect, neutralizing antibodies and immune defense mechanism would have an important role in delaying onset of clinical symptoms and mitigate the severity of infection.
HIVs exhibit a high degree of genetic polymorphism which results in widespread antigenic variability and in different patterns of virus infection and cytopathogenicity in culture and possibly in vivo. Whether and how these features influence the course of AIDS the syndrome caused by HIV, is basically unknown. It is thus mandatory to elucidate the role played by the viral heterogeneity in determining the course of the disease and its variable pattern in different areas of the world. It may also be important to know whether AIDS patients can exhibit a double or possibly multiple infection by several HIVs and how this modifies the features of the syndrome. The description and the understanding of the mechanism(s) underlying the pronounced variability of HIV is the focus of this collaborative research effort.

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias biológicas › microbiología › virología
• ciencias naturales › ciencias biológicas › genética › ADN
• ciencias médicas y de la salud › ciencias de la salud › salud pública y medio ambiental › epidemiología
• ciencias médicas y de la salud › medicina básica › inmunología
• ciencias médicas y de la salud › ciencias de la salud › enfermedad infecciosa › virus de ARN › VIH

Programa(s)

• FP2-MHR 4C - Research and development coordination programme (EEC) in the field of medical and health research, 1987-1991

Tema(s)

• 1.2 - Viro-immunological research (basic research)

Convocatoria de propuestas

Datos no disponibles

Régimen de financiación

CON - Coordination of research actions

Coordinador

Seminario Romano Ricerche sul Cancro

• Aportación de la UE: Sin datos
• Dirección: Via G.D. Romagnosi 20 ; 00196 Roma ; Italia
• Coste total: Sin datos