Proteases of HIV-1 and MAV Hydrolyze Specifically Human Apo-Hemopexin

2000 ◽  
Vol 65 (7) ◽  
pp. 1191-1197
Author(s):  
Ivan Kluh ◽  
Věra Černá ◽  
Iva Pichová ◽  
Zdeněk Voburka

The specificities of HIV-1 (Human Immunodeficiency Virus Type 1) and MAV (Myeloblastosis Associated Virus) proteases have been evaluated for their ability to split two-domain protein human apo-hemopexin. Both proteases hydrolyze only one peptidic bond Leu240-Ser241located in the connecting region between two domains. The ability of viral proteases to cleave Leu-Ser bond was confirmed by cleavage of synthetic octapeptide His-Leu-Val-Leu-Ser-Ala-Leu-Thr-NH2covering the susceptible area of human apo-hemopexin. The results demonstrate that the cleavage of Leu-Ser bond is not due to its location in the interdomain region of apo-hemopexin. The cleavable bond Leu-Ser has never been found either in viral or in non-viral proteins. According to the vector projection method this octapeptide was considered as non-hydrolyzable.

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2480-2488 ◽  
Author(s):  
M Semmel ◽  
A Macho ◽  
D Coulaud ◽  
A Alileche ◽  
S Plaisance ◽  
...  

Abstract HL-60 cells infected with human immunodeficiency virus type 1 (HIV 1) can be induced to differentiate along the granulocyte pathway by retinoic acid. In these cells, HIV mRNA synthesis is stimulated, but synthesis of viral proteins and virus replication are blocked and HIV- infected cells die after becoming apoptotic and/or vacuolized.


Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2480-2488
Author(s):  
M Semmel ◽  
A Macho ◽  
D Coulaud ◽  
A Alileche ◽  
S Plaisance ◽  
...  

HL-60 cells infected with human immunodeficiency virus type 1 (HIV 1) can be induced to differentiate along the granulocyte pathway by retinoic acid. In these cells, HIV mRNA synthesis is stimulated, but synthesis of viral proteins and virus replication are blocked and HIV- infected cells die after becoming apoptotic and/or vacuolized.


1994 ◽  
Vol 70 (6) ◽  
Author(s):  
Marisa Márcia Mussi-Pinhata ◽  
Maria Célia C. Ferez ◽  
Dimas T. Covas ◽  
Geraldo Duarte ◽  
Márcia L. Isaac ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1798
Author(s):  
Grant R. Campbell ◽  
Stephen A. Spector

Effective antiretroviral therapy has led to significant human immunodeficiency virus type 1 (HIV-1) suppression and improvement in immune function. However, the persistence of integrated proviral DNA in latently infected reservoir cells, which drive viral rebound post-interruption of antiretroviral therapy, remains the major roadblock to a cure. Therefore, the targeted elimination or permanent silencing of this latently infected reservoir is a major focus of HIV-1 research. The most studied approach in the development of a cure is the activation of HIV-1 expression to expose latently infected cells for immune clearance while inducing HIV-1 cytotoxicity—the “kick and kill” approach. However, the complex and highly heterogeneous nature of the latent reservoir, combined with the failure of clinical trials to reduce the reservoir size casts doubt on the feasibility of this approach. This concern that total elimination of HIV-1 from the body may not be possible has led to increased emphasis on a “functional cure” where the virus remains but is unable to reactivate which presents the challenge of permanently silencing transcription of HIV-1 for prolonged drug-free remission—a “block and lock” approach. In this review, we discuss the interaction of HIV-1 and autophagy, and the exploitation of autophagy to kill selectively HIV-1 latently infected cells as part of a cure strategy. The cure strategy proposed has the advantage of significantly decreasing the size of the HIV-1 reservoir that can contribute to a functional cure and when optimised has the potential to eradicate completely HIV-1.


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