Experimental study of possible involvement of some apoptosis mechanisms in pathogenesis of the HIV infection: 2. The CD4+ T lymphocytes depletion in the HIV infection occurs through activation-induced apoptosis.

The present work is a part of a complex experimental study aimed at the demonstration of the two previously published hypotheses regarding the involvement of apoptosis in general in the viral infection and especially in HIV infection (1). Our researches have shown that the significant lowering of the number of peripheral CD4+ T lymphocytes in HIV-infected children is associated with a marked increase of the soluble interleukin 2-receptor (sIL2-R)# concentration, in comparison with HIV-negative, healthy or acute infections exhibiting controls. As sIL-2R is a circulating marker of cell activation, we investigated the role of monocytes (antigen-presenting cells) in the viability of peripheral lymphocytes isolated from HIV-infected children in comparison with the controls. Lymphocytes cultivation in the absence and in the presence of autologous monocytes led to the following conclusions: 1) freshly isolated lymphocytes from HIV-positive individuals undergo an accelerated spontaneous apoptosis in comparison with that of lymphocytes isolated from HIV-negative individuals: 2) the normal antiapoptotic effect of monocytes on lymphocytes diminishes gradually in the HIV infection, changing into a proapoptotic effect, corresponding to the sIL-2R augmentation to increasingly higher values. Our results show that peripheral CD4+ T-lymphocyte depletion in HIV infection occurs through apoptosis and the activation-induced cell death is one of the possible apoptosis mechanisms.

Experimental study of the possible implications of some apoptosis mechanisms in the pathogenesis of HIV infection. 1. In vitro apoptotic death of peripheral blood lymphocytes.

The human immunodeficiency virus (HIV) infection produces a gradual depletion of T-helper CD4+ lymphocytes as, surprisingly, a consequence of apoptosis of the uninfected lymphocytes. We suggested that this is the result of the action exerted by HIV inductors of apoptosis (for example, gp 120) in the absence of viral apoptosis suppressor, which confers protection to the infected cell. We intended to demonstrate this hypothesis within the framework of a complex study regarding the apoptosis mechanisms in HIV infection. We started this study by setting up an apoptosis model on HIV-negative peripheral blood lymphocytes (PBLs)* cultivated in vitro in the presence of dexamethasone (Dex). In this work we characterize this model morphologically and biochemically. Three unreported morphological changes observed by us--namely: I) fringing of nucleus with advancement of fringes up to the plasma membrane; II) segmentation and peripheral migration of condensed chromatin through a rotation movement; III) "flowering of the cell" consisting in the radial separation of the lymphocyte into centrally united "petals" with the tendency to form apically multiple apoptotic bodies--completed the classical morphology of the apoptosis phenomenon. The apoptotic death was confirmed by the oligonucleosomal (multiples of 200 bp) and mononucleosomal fragmentation of DNA isolated from lymphocytes.

Studies concerning the course of some acute respiratory diseases in nine districts of south-east area of Romania between November 1994 and April 1995. Epidemiological, virological and serological data.

A moderate level of morbidity through acute respiratory diseases (ARD), of the upper tract, viral pneumonia and clinical influenza was recorded during November 1994 and April 1995 in the South-East area of Romania (nine districts). By virological and serological investigation adenosyncytial respiratory, parainfluenza type 3 and influenza type B viruses were found to be the most frequent etiological agents of these infections which affected especially the babies and the children of 1-14 years of age. Sporadic influenza outbreaks were noticed from which influenza strains of virus were isolated, antigenically related to the prototype strain A/Johannesburg 33/94.

The evidence of circulation of some viruses in a great town of Romania during the first half of 1992.

Complex serological survey performed in the town B. during the first half of 1992 emphasized an active circulation of some respiratory viruses, especially of parainfluenza type 3 and 1, influenza subtypes A(H3N2) and A(H1N1), adeno and syncytial respiratory as well as of Mycoplasma pneumoniae. Less important was the frequence of antibodies against Chlamydia psittaci, East equine, West Nile and tick-borne encephalitis as well as parainfluenza type 2 and influenza type B viruses.

Epidemiological, viral and serological studies concerning the evolution of some acute respiratory diseases between November 1992 and March 1993 in nine districts of the south-east area of Romania.

Viral and serological studies led to the conclusion that parainfluenza type 3 and influenza type A(H3N2) viruses were the most implicated in the etiology of acute respiratory diseases (ARD), viral pneumonia and clinical influenza in nine districts of the south-east area of Romania during the November 1992--March 1993 period. Epidemiological survey pointed on the 0-1 year group of age as the most affected by the above mentioned respiratory diseases.

Epidemiological, viral and serological studies concerning the evolution of some acute respiratory diseases between November 1992 and March 1993 in nine districts of the south-east area of Romania.

Viral and serological studies led to the conclusion that parainfluenza type 3 and influenza type A(H3N2) viruses were the most implicated in the etiology of acute respiratory diseases (ARD), viral pneumonia and clinical influenza in nine districts of the south-east area of Romania during the November 1992-March 1993 period. Epidemiological survey pointed on the 0-1 year group of age as the most affected by the above mentioned respiratory diseases.

Considerations about the possible function of ceruloplasmin in influenza and parainfluenza virus infections.

The experimental data reveal that ceruloplasmin is a serum nonspecific factor acting during the early and late stages of infection with some respiratory viruses. This complex action seems to be based both on the enzymatic activity and on the copper-glycoprotein structure of ceruloplasmin. The changes in progen antigenicity produced by ceruloplasmin are probably involved in the mechanism of the antigenic shift and drift.