V3 loop-derived multibranched peptides as inhibitors of HIV infection in CD4+ and CD4− cells

1996 ◽  
Vol 5 (1) ◽  
pp. 243-250 ◽  
Author(s):  
Jacques Fantini ◽  
Nouara Yahi ◽  
Kamel Mabrouk ◽  
Hervé Rochat ◽  
Jurphaas van Rietschoten ◽  
...  
Keyword(s):  
V3 Loop ◽  
Morphologia ◽  
2021 ◽  
Vol 15 (3) ◽  
pp. 109-118
Author(s):  
I.V. Liskina ◽  
L.M. Zagaba

Background. The progression of HIV infection is accompanied by the development of opportunistic diseases, including pleural effusions of various origins. Morphological examination of pleura tissue in cases of pleural effusion serves as the basis for establishing the etiology of the pathological process and, therefore, the final clinical diagnosis. Objective – analysis of results of morphological diagnostics of pleura lesions in HIV-infected patients in comparison with other laboratory tests and clinical diagnosis. Methods. 103 cases of pleurisy of various origins were studied. Pleural biopsies were obtained by various types of minimally invasive diagnostic interventions with subsequent morphological examination. Results were compared with the available data of microbiological and molecular genetic studies of pleural biopsies. Results. At the time of hospitalization the preliminary clinical diagnosis was pleurisy of unknown etiology in 96,1 % of cases. A combined disease was diagnosed – hepatitis C in a third of all observations according to the results of laboratory tests. Due to routine staining with hematoxylin and eosin, tuberculosis lesions of the pleura were diagnosed in 59,2 %, the second most frequent was the diagnosis of nonspecific pleurisy, 20,4 %. According to the duration of the process, acute pleural tuberculosis was established in 19,7 % of cases, the subacute form of tuberculosis pleurisy – in 54,1 % of cases, and chronic pleural tuberculosis was established in 22,9 % of cases. In 17,5 % of cases, in order to clarify the etiology of pleurisy, additional histochemical staining for infectious agents was performed. The results of microbiological and molecular genetic studies were established in 76,7 % of cases. The greatest number of M. tuberculosis detection was obtained during the culture study of the biopsy material and exudates. When comparing the final clinical diagnosis and the level of CD4 cells in peripheral blood, it was found that in most cases (74,5 %) pleural effusions developed at low counts of CD4 cells, less than 350/l. Conclusion. Tuberculosis predominates in the etiological structure of pleural effusions in patients with HIV infection. Pleural tuberculosis can be the main secondary disease or be combined with pulmonary tuberculosis. In second place in terms of frequency of occurrence, nonspecific pleurisy was diagnosed as a complication of the main secondary disease. Pleural effusions develop when CD4 cell counts are low. Morphological diagnostics of pleural lesions is the main research method in the diagnostic algorithm of cases of pleural effusions of unknown etiology against the background of HIV infection.


2015 ◽  
Vol 90 (2) ◽  
pp. 636-649 ◽  
Author(s):  
Susan Zolla-Pazner ◽  
Sandra Sharpe Cohen ◽  
David Boyd ◽  
Xiang-Peng Kong ◽  
Michael Seaman ◽  
...  

ABSTRACTAntibodies (Abs) specific for the V3 loop of the HIV-1 gp120 envelope neutralize most tier 1 and many tier 2 viruses and are present in essentially all HIV-infected individuals as well as immunized humans and animals. Vaccine-induced V3 Abs are associated with reduced HIV infection rates in humans and affect the nature of transmitted viruses in infected vaccinees, despite the fact that V3 is often occluded in the envelope trimer. Here, we link structural and experimental data showing how conformational alterations of the envelope trimer render viruses exceptionally sensitive to V3 Abs. The experiments interrogated the neutralization sensitivity of pseudoviruses with single amino acid mutations in various regions of gp120 that were predicted to alter packing of the V3 loop in the Env trimer. The results indicate that the V3 loop is metastable in the envelope trimer on the virion surface, flickering between states in which V3 is either occluded or available for binding to chemokine receptors (leading to infection) and to V3 Abs (leading to virus neutralization). The spring-loaded V3 in the envelope trimer is easily released by disruption of the stability of the V3 pocket in the unliganded trimer or disruption of favorable V3/pocket interactions. Formation of the V3 pocket requires appropriate positioning of the V1V2 domain, which is, in turn, dependent on the conformation of the bridging sheet and on the stability of the V1V2 B-C strand-connecting loop.IMPORTANCEThe levels of antibodies to the third variable region (V3) of the HIV envelope protein correlate with reduced HIV infection rates. Previous studies showed that V3 is often occluded, as it sits in a pocket of the envelope trimer on the surface of virions; however, the trimer is flexible, allowing occluded portions of the envelope (like V3) to flicker into an exposed position that binds antibodies. Here we provide a systematic interrogation of mechanisms by which single amino acid changes in various regions of gp120 (i) render viruses sensitive to neutralization by V3 antibodies, (ii) result in altered packing of the V3 loop, and (iii) activate an open conformation that exposes V3 to the effects of V3 Abs. Taken together, these and previous studies explain how V3 antibodies can protect against HIV-1 infection and why they should be one of the targets of vaccine-induced antibodies.


1995 ◽  
Vol 181 (1) ◽  
pp. 423-428 ◽  
Author(s):  
R Paganelli ◽  
E Scala ◽  
I J Ansotegui ◽  
C M Ausiello ◽  
E Halapi ◽  
...  

Increased levels of serum IgE and eosinophilia have been described in human immunodeficiency virus (HIV) infection, almost exclusively in patients with CD4+ cell count < 200 cells/microliters. IgE production is regulated by CD4+ T helper type 2 (Th-2) lymphocytes, producing interleukin 4 (IL-4) and expressing a ligand for the B cell-specific CD40 molecule (CD40 ligand [L]). A shift to a Th-2-like pattern of cytokine secretion has been postulated to be associated with progression toward acquired immunodeficiency syndrome (AIDS). We studied three AIDS patients with very high levels of IgE and almost complete depletion of CD4+ lymphocytes, suggesting that IgE synthesis could not be driven by CD4+ cells. IgE in vitro synthesis by cells from such patients was, however, inhibited by anti-IL-4. We show that both CD8+ T cell lines and the majority of CD8+ T cells clones derived from these patients produce IL-4, IL-5, and IL-6 in half of the cases together with interferon gamma (IFN-gamma). 44% of CD8+ T cell clones expressed a CD40L, and the supernatants of the clones were capable of inducing IgE synthesis by normal B cells costimulated with anti-CD40. CD8+ T cells in these patients therefore functionally mimic Th-2 type cells and may account for hyper-IgE and eosinophilia in the absence of CD4+ cells. The presence of such CD8+ cells may also provide a source of IL-4 directing the development of predominant Th-2 responses in HIV infection.


Background of study: There is emerging evidence that human immunodeficiency virus (HIV) infection, even in the absence of anti-retroviral therapy (ART) toxicity and other cofactors, may have a direct impact on liver pathogenesis. Aim: Based on this premise, our study determined the impact of HIV infection on liver enzymes as markers of hepatic function. Methods: the case-control study comprised of a total of 60 participants (30 males and 30 females) aged 18-60 years. The study compared aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), cluster of differentiation (CD4+) cells among ART-naïve HIV patients (n=20), follow-up HIV patients who were on highly active ART (n=20) and apparently healthy controls (n=20). Results: a significant (P<0.05) change was observed in the liver enzymes and CD4+ cells among the study groups compared. Specific changes showed that serum AST, ALP levels of ART-naïve patients were significantly (P<0.05) higher than that of follow-up and controls. Serum ALT levels of controls were significantly (P<0.01) lower than that of ART-naïve and follow-up patients. The CD4+ cell count of ART-naïve patients was significantly (P=0.000) lower than that of follow-up and control groups. Conclusion: Liver enzyme abnormalities were observed in ART naïve HIV infected patients. Consequently, there is a need to monitor liver enzyme levels before and after initiation of therapy.


2017 ◽  
Vol 12 (5) ◽  
pp. 78-98
Author(s):  
A. Tridane ◽  
B. El Boukari ◽  
K. Hattaf ◽  
N. Yousfi

Author(s):  
Marek Malecki ◽  
Bianka Saetre

Abstract: HIV viremia is the essential element for progression of an initial HIV infection into AIDS and death. The currently approved management relies primarily on chemotherapy repressing the HIV replication in the infected CD4+ cells, although with severe systemic adverse effects. The problem is that it does not physically eliminate viruses, which then not only keep infecting healthy cells of these patients, but also promote infectivions of other people.  


1999 ◽  
Vol 15 (4) ◽  
pp. 381-390 ◽  
Author(s):  
Nabila Seddiki ◽  
Sebastien Nisole ◽  
Bernard Krust ◽  
Christian Callebaut ◽  
Gilles Guichard ◽  
...  

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