Despite the success of highly active antiretroviral therapy (HAART), integrated HIV-1 proviral DNA cannot be eradicated from an infected individual. HAART is not able to eliminate latently infected cells that remain invisible to the immune system. Viral sanctuaries in specific tissues and immune-privileged sites may cause residual viral replication that contributes to HIV-1 persistence. The "Shock or Kick, and Kill" approach uses latency reversing agents (LRAs) in the presence of HAART, followed by cell-killing due to viral cytopathic effects and immune-mediated clearance. Different LRAs may be required for the in vivo reactivation of HIV-1 in different CD4 T cell reservoirs, leading to the activation of cellular transcription factors acting on the integrated proviral HIV-1 LTR. An important requirement for LRA drugs is the reactivation of viral transcription and replication without causing a generalized immune activation. Toll-like receptors, RIG-I like receptors, and STING agonists have emerged recently as a new class of LRAs that augment selective apoptosis in reactivated T lymphocytes. The challenge is to extend in vitro observations to HIV-1 positive patients. Further studies are also needed to overcome the mechanisms that protect latently infected cells from reactivation and/or elimination by the immune system. The Block and Lock alternative strategy aims at using latency promoting/inducing agents (LPAs/LIAs) to block the ability of latent proviruses to reactivate transcription in order to achieve a long term lock down of potential residual virus replication. The Shock and Kill and the Block and Lock approaches may not be only alternative to each other, but, if combined together (one after the other), or given all at once [namely "Shoc-K(kill) and B(block)-Lock"], they may represent a better approach to a functional cure.
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http://dx.doi.org/10.3390/pathogens10111517 | DOI Listing |
J Med Virol
December 2024
Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.
Emerging evidence underscores the pivotal role of long noncoding RNAs (lncRNAs) as crucial regulators within the HIV life cycle. However, the precise functions and detailed mechanisms by which lncRNAs operate in HIV-1 highly exposed but persistently seronegative (HESN) individuals remain currently unknown. Through RNA sequencing analysis of the HESN individual and the matched control, we identified potential lncRNAs.
View Article and Find Full Text PDFNeurol Neuroimmunol Neuroinflamm
January 2025
Department of Neurology, University of Pennsylvania, Philadelphia.
During the past decade (and beyond), neurologists have become aware of the emergence, persistence, and consequences of some familiar and new infections affecting the nervous system. Even among the familiar CNS infections, such as herpes virus, polyoma virus/JC, influenza, arbovirus, and hepatitis, challenges remain in developing effective antiviral treatments and treatments of postinfection sequelae. With the changing environment and increased global travel, arthropod vectors that mediate zoonotic disease transmission have spread unfamiliar viruses such as West Nile virus, dengue, chikungunya, equine encephalitis, and Zika, among others.
View Article and Find Full Text PDFJ Acquir Immune Defic Syndr
January 2025
Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (INI-Fiocruz), Rio de Janeiro, Brazil ; and.
Background: The COVID-19 pandemic had great impact on HIV care and prevention worldwide, including in Brazil. We compared HIV testing, recent infection, and annualized incidence according to the COVID-19 pandemic period among cisgender men who have sex with men (MSM) and transgender women (TGW).
Setting: HIV and sexually transmitted infection testing, prevention, and treatment referral service in Rio de Janeiro, Brazil.
JCI Insight
December 2024
Graduate Program in Immunology, University of Michigan, Ann Arbor, United States of America.
Despite effective treatment, Human immunodeficiency virus (HIV) persists in optimally treated people as a transcriptionally silent provirus. Latently infected cells evade the immune system and the harmful effects of the virus, thereby creating a long-lasting reservoir of HIV. To gain a deeper insight into the molecular mechanisms of HIV latency establishment, we constructed a series of HIV-1 fluorescent reporter viruses that distinguish active versus latent infection.
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