Beyond retrovirus infection: HIV meets gene therapy

The human immunodeficiency virus (HIV) is classified as a retrovirus because of its RNA genome and the fact that it requires reverse transcriptase to convert it into DNA. This virus belongs to the lentivirinae subfamily and is able to infect quiescent cells but is better known for its association with acquired immunodeficiency syndrome (AIDS) and can be described as one of the most effective vectors for gene transfer. Biosafety concerns are present whenever viral vectors are employed but are particularly pertinent to the development of HIV-based vectors. Insertional mutagenesis and the production of new replication-competent viruses (RCV) have been pointed to as major problems, but experimental data have shown that safe protocols can be developed for their production and application. Virological, evolutionary, immunological and cell biology studies must be conducted jointly to allow the clinical use of HIV vectors. This review will focus on the general properties, production and applications of retrovectors in gene therapy, with particular emphasis on those based on HIV systems.

Characterization of two infectious mouse mammary tumour viruses: superantigenicity and tumorigenicity.

Mouse mammary tumour virus (MMTV) is a type B retrovirus that causes mammary tumours in susceptible mice. MMTV encodes a superantigen (SAg) that has the property of stimulating T-cell populations expressing a particular variable region of the T-cell receptor (TCR) beta chain (Vbeta) and needs to be presented in the context of major histocompatibility complex (MHC) class II molecules. Previously, we described two exogenous MMTV, MMTV BALB14, which encodes a superantigen that induces the deletion of Vbeta14+ Tcells, and MMTV BALB2, which encodes a SAg that induces the deletion of Vbeta2+ Tcells. We now describe their biological activity: the deletions involve both CD4+ and CD8+ populations, are progressive and can be detected in blood, lymph nodes and spleen. Such deletions reflect, at least in part, those occurring during intrathymic development. Both BALB2 and BALB14 viral variants are capable of inducing a strong increase of Vbeta-specific T cells in BALB/c mice (I-A+, I-E+). However, when injected into the footpad, their initial stimulatory capacity differs in that the presence of MHC I-E molecules is essential only for the stimulation of Vbeta2+ T cells. Both viral variants are able to induce deletion even in the absence of the I-E molecule in which case, however, deletion appears later and is less pronounced. Both exogenous MMTVs induce, at the end of a year, 30-35% of pregnancy-dependent mammary adenocarcinomas.

Síndrome retroviral agudo / Acute retroviral syndrome: case report

A 37 years old male developed fever for 20 days, along with headache, anorexia malaise, sweating, pharyngitis, lymphadenopathy and splenomegaly. At this stage, Ag p 24 was positive and anti HIV was negative. The patient recovered fully but 6 monts later positive HIV titers were demonstrated by immunofluorescence and Westernblot. A retrospective HIV titers were demonstrated by immunofluorescence and Westernblot. A retrospective diagnosis of acute retroviral syndrome was made. The dioddicult

Leukaemia mortality in Trinidad and Tobago 1957-1976.

Leukaemia mortality in Trinidad and Tobago over the period 1957-1976 was reviewed. The mortality rate was stable except for an unexplained drop in the adult leukaemia mortality in 1966/67. Throughout the period, annual deaths due to leukaemia were less than one percent of the total annual deaths from all causes. The age and sex patterns of leukaemia mortality were similar to that of the United States of America but the overall mortality rate of 24 per million was low when compared with that of the USA where the rate in 1971 was 70 per million.