scholarly journals Clearance of HIV infection by selective elimination of host cells capable of producing HIV

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Min Li ◽  
Wei Liu ◽  
Tonya Bauch ◽  
Edward A. Graviss ◽  
Roberto C. Arduino ◽  
...  

AbstractThe RNA genome of the human immunodeficiency virus (HIV) is reverse-transcribed into DNA and integrated into the host genome, resulting in latent infections that are difficult to clear. Here we show an approach to eradicate HIV infections by selective elimination of host cells harboring replication-competent HIV (SECH), which includes viral reactivation, induction of cell death, inhibition of autophagy and the blocking of new infections. Viral reactivation triggers cell death specifically in HIV-1-infected T cells, which is promoted by agents that induce apoptosis and inhibit autophagy. SECH treatments can clear HIV-1 in >50% mice reconstituted with a human immune system, as demonstrated by the lack of viral rebound after withdrawal of treatments, and by adoptive transfer of treated lymphocytes into uninfected humanized mice. Moreover, SECH clears HIV-1 in blood samples from HIV-1-infected patients. Our results suggest a strategy to eradicate HIV infections by selectively eliminating host cells capable of producing HIV.

2007 ◽  
Vol 14 (4) ◽  
pp. 391-396 ◽  
Author(s):  
Dong Sung An ◽  
Betty Poon ◽  
Raphael Ho Tsong Fang ◽  
Kees Weijer ◽  
Bianca Blom ◽  
...  

ABSTRACT The goal of this study was to develop a small-animal model to study human immunodeficiency virus type 1 (HIV-1) pathogenesis in blood and primary and secondary lymphoid organs. Rag2−/−γc −/− mice that are neonatally injected with human CD34+ cells develop a functional human immune system (HIS), with human hematopoietic cells being found in the thymuses, peripheral blood, spleens, and bone marrow of the animals (hereafter these animals are referred to as HIS-Rag2−/−γc −/− mice). HIS-Rag2−/−γc −/− mice were infected with small amounts of CCR5-tropic HIV-1. Viral replication and immunophenotypic changes in the human cells in peripheral blood and lymphoid organs were examined. The productive infection of human cells in peripheral blood, thymus and spleen tissue, and bone marrow was detected. Ratios of CD4+ T cells to CD8+ T cells in the infected animals declined. Although no specific anti-HIV-1 immune responses were detected, immunoglobulin M (IgM) and IgG antibodies to an unidentified fetal calf serum protein present in the virus preparation were found in the inoculated animals. Thus, we have shown that the HIS-Rag2−/−γc −/− mouse model can be used for infection with low doses of CCR5-tropic HIV-1, which is most commonly transmitted during primary infections. HIS-Rag2−/−γc −/− mice can serve as a small-animal model for investigating HIV-1 pathogenesis and testing potential HIV-1 therapies, and studies with this model may replace some long and costly studies with nonhuman primates.


2005 ◽  
Vol 13 (3-4) ◽  
pp. 126-130
Author(s):  
Nevena Veljkovic

A broad range of similarities between HIV-1 gp120 and human proteins-especially those participating in immune responses-highlight gp120 as a pleiotropic protein which can influence many important functions of the human immune system. The molecular mimicry that serves to the human immunodeficiency virus as potent destructive arms against immune system could be the weak point we are in search of over decades. Examples involving sequence and informational similarities of HIV-1 gp120 and immunerelated host cell proteins important for prevention and treatment of HIV infection are presented. .


2008 ◽  
Vol 82 (18) ◽  
pp. 9154-9163 ◽  
Author(s):  
Yan Zhou ◽  
Lin Shen ◽  
Hung-Chih Yang ◽  
Robert F. Siliciano

ABSTRACT CD4+ T-cell depletion is the hallmark of AIDS pathogenesis. Multiple mechanisms may contribute to the death of productively infected CD4+ T cells and innocent-bystander cells. In this study, we characterize a novel mechanism in which human immunodeficiency virus type 1 (HIV-1) infection preferentially depletes peripheral memory CD4+ T cells before the completion of reverse transcription. Using a recombinant HIV-1 carrying the green fluorescent protein reporter gene, we demonstrate that memory CD4+ T cells were susceptible to infection-induced cell death at a low multiplicity of infection. Infected memory CD4+ T cells underwent rapid necrotic cell death. Killing of host cells was dependent on X4 envelope-mediated viral fusion, but not on virion-associated Vpr or Nef. In contrast to peripheral resting CD4+ T cells, CD4+ T cells stimulated by mitogen or certain cytokines were resistant to HIV-1-induced early cell death. These results demonstrate that early steps in HIV-1 infection have a detrimental effect on certain subsets of CD4+ T cells. The early cell death may serve as a selective disadvantage for X4-tropic HIV-1 in acute infection but may play a role in accelerated disease progression, which is associated with the emergence of X4-tropic HIV-1 in the late stage of AIDS.


Coronaviruses ◽  
2021 ◽  
Vol 02 ◽  
Author(s):  
Latifa Khattabi ◽  
Mustapha Mounir Bouhenna ◽  
Feriel Sellam

: The present paper elucidates the conceivable application of two key molecules in SARS-CoV-2 detection of suspected infected persons. These molecules were selected from the basis of ACE-2 and S protein strong interaction that allows virus attachment to its host cells, on the other hand specific immunocompetant effectors generated by human immune system during the infection. Several testing procedures are already used to diagnose SARS-CoV-2 infection, particularly RT-PCR technique. ELISA and LFIA are possible assays for the employment of shACE-2/ hAc-anti-S (the molecules of interest) as the main agents of the test and confer a dual principal functions (capture and detection). The future diagnostic kits involving shACE-2 and hAc-anti-S will have the particularity of high sensitivity and rapid detection in addition to its advantage of relatively easy conception. It could be largely considered as a technical advanced kits in regards to the current SARS-CoV-2 diagnostic immunoassays.


2005 ◽  
Vol 79 (5) ◽  
pp. 3195-3199 ◽  
Author(s):  
Jean-Daniel Lelièvre ◽  
Frédéric Petit ◽  
Damien Arnoult ◽  
Jean-Claude Ameisen ◽  
Jérôme Estaquier

ABSTRACT Fas-mediated T-cell death is known to occur during human immunodeficiency virus (HIV) infection. In this study, we found that HIV type 1 LAI (HIV-1LAI) primes CD8+ T cells from healthy donors for apoptosis, which occurs after Fas ligation. This effect is counteracted by a broad caspase inhibitor (zVAD-fmk). Fas-mediated cell death does not depend on CD8+ T-cell infection, because it occurred in the presence of reverse transcriptase inhibitors. However, purified CD8+ T cells are sensitive to Fas only in the presence of soluble CD4. Finally, we found that interleukin 7 (IL-7) increases Fas-mediated CD4+ and CD8+ T-cell death induced by HIV-1LAI. Since high levels of IL-7 are a marker of poor prognosis during HIV infection, our data suggest that enhancement of Fas-mediated T-cell death by HIV-1LAI and IL-7 is one of the mechanisms involved in progression to AIDS.


2020 ◽  
Vol 11 (3) ◽  
pp. 4866-4871
Author(s):  
Thualfakar Hayder Hasan ◽  
Raad A. Al-Harmoosh ◽  
Huda Jameel Baker Al-khilkhali

Acquired Immune Deficiency Syndrome (ADIS) is a disease of the human immune system that results in a decline in the efficiency of the human immune system step by step to leave people exposed to many infections and tumours. It caused by the Human Immunodeficiency Virus (HIV). The first appeared of HIV in West Central Africa in the late 19th or early 20th century. The direct contact from personal mucus membrane or bloodstream and physical fluid (blood, vaginal semen fluid and breastfeeding milk) containing the virus is the unique viral transmission route. Out of 80 blood samples were taken from different areas of Najaf city, Iraq, for ages from 20 to 60 years (males and females) to the period from 1/1/2019 to 19/12/2019. The surface antigen of the HIV was detected by the ELISA technique and mini VIDAS by a virus-specific kit. Out of 80 different patients by physical examination infected with ADIS: HIV viruses were the most incidences with 12 isolates (15%) while, there were 66 isolates (82.5%) were belonged to other infections and two strains (2.5%) were negative to any viral infection.


2008 ◽  
Vol 82 (14) ◽  
pp. 7022-7033 ◽  
Author(s):  
Terrence M. Dobrowsky ◽  
Yan Zhou ◽  
Sean X. Sun ◽  
Robert F. Siliciano ◽  
Denis Wirtz

ABSTRACT The fusion of human immunodeficiency virus type 1 (HIV-1) to host cells is a dynamic process governed by the interaction between glycoproteins on the viral envelope and the major receptor, CD4, and coreceptor on the surface of the cell. How these receptors organize at the virion-cell interface to promote a fusion-competent site is not well understood. Using single-molecule force spectroscopy, we map the tensile strengths, lifetimes, and energy barriers of individual intermolecular bonds between CCR5-tropic HIV-1 gp120 and its receptors CD4 and CCR5 or CXCR4 as a function of the interaction time with the cell. According to the Bell model, at short times of contact between cell and virion, the gp120-CD4 bond is able to withstand forces up to 35 pN and has an initial lifetime of 0.27 s and an intermolecular length of interaction of 0.34 nm. The initial bond also has an energy barrier of 6.7 kB T (where kB is Boltzmann's constant and T is absolute temperature). However, within 0.3 s, individual gp120-CD4 bonds undergo rapid destabilization accompanied by a shortened lifetime and a lowered tensile strength. This destabilization is significantly enhanced by the coreceptor CCR5, not by CXCR4 or fusion inhibitors, which suggests that it is directly related to a conformational change in the gp120-CD4 bond. These measurements highlight the instability and low tensile strength of gp120-receptor bonds, uncover a synergistic role for CCR5 in the progression of the gp120-CD4 bond, and suggest that the cell-virus adhesion complex is functionally arranged about a long-lived gp120-coreceptor bond.


Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 909
Author(s):  
Ighor Arantes ◽  
Myuki Alfaia Esashika Crispim ◽  
Mônica Nogueira da Guarda Reis ◽  
Mariane Martins Araújo Stefani ◽  
Gonzalo Bello

Non-pandemic variants of the Human Immunodeficiency Virus Type 1 (HIV-1) subtype B accounts for a significant fraction of HIV infections in several Caribbean islands, Northeastern South American countries and the Northern Brazilian states of Roraima and Amazonas. In this paper, we used a comprehensive dataset of HIV-1 subtype B pol sequences sampled in Amazonas and Roraima between 2007 and 2017 to reconstruct the phylogeographic and demographic dynamics of the major HIV-1 subtype B non-pandemic Brazilian lineage, designated as BCAR-BR-I. Our analyses revealed that its origin could be traced to one of many viral introductions from French Guiana and Guyana into Northern Brazil, which probably occurred in the state of Amazonas around the late 1970s. The BCAR-BR-I clade was rapidly disseminated from Amazonas to Roraima, and the epidemic grew exponentially in these Northern Brazilian states during the 1980s and 1990s, coinciding with a period of economic and fast population growth in the region. The spreading rate of the BCAR-BR-I clade, however, seems to have slowed down since the early 2000s, despite the continued expansion of the HIV-1 epidemic in this region in the last decade.


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