Related Experiment Video

Updated: Jul 2, 2026

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication
10:12

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication

Published on: June 14, 2024

Erythromycin derivatives inhibit HIV-1 replication in macrophages through modulation of MAPK activity to induce small

Iwao Komuro1, Toshiaki Sunazuka, Kiyoko S Akagawa

  • 1Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.

Proceedings of the National Academy of Sciences of the United States of America
|August 23, 2008
PubMed

Insights

Erythromycin A derivatives EM201 and EM703 can transform HIV-1 susceptible macrophages into resistant ones. These drugs offer potential for new AIDS treatments by inhibiting viral replication and MAPK activation.

Area of Science:

  • Immunology
  • Virology
  • Pharmacology

Background:

  • Macrophages (MPhis) are key reservoirs for HIV-1, particularly in tuberculosis patients.
  • Distinct MPhis exhibit varying susceptibility to HIV-1, influenced by hematopoietic cell kinase (Hck) and CCAAT enhancer binding protein beta (C/EBPbeta) isoforms.

Purpose of the Study:

  • To investigate the potential of Erythromycin A (EMA) derivatives, EM201 and EM703, in modulating MPhis susceptibility to HIV-1.
  • To elucidate the mechanisms by which EM201 and EM703 confer HIV-1 resistance to MPhis.

Main Methods:

  • Assessing the effect of EM201 and EM703 on HIV-1 replication in tissue MPhis.
  • Analyzing the expression of Hck and C/EBPbeta isoforms in response to EMA derivatives.
  • Investigating the role of mitogen-activated protein kinase (MAPK) pathways, including p38MAPK and ERK1/2, in MPhis susceptibility and drug response.

Main Results:

  • EM201 and EM703 effectively inhibit HIV-1 replication in tissue MPhis by down-regulating Hck and inducing inhibitory small C/EBPbeta isoforms.
  • These EMA derivatives suppress p38MAPK activation, which is characteristic of HIV-1 susceptible MPhis.
  • EM201 and EM703 counteract the viral replication boost induced by CD4(+)T cell interaction with MPhis by inhibiting MAPK activation.

Conclusions:

  • EM201 and EM703 convert HIV-1 susceptible MPhis to a resistant state, offering a novel therapeutic strategy.
  • These compounds show promise for controlling residual HIV-1 in the lymphoreticular system and developing new anti-HIV drugs for AIDS patients.

More Related Videos

Isolation, Transfection, and Culture of Primary Human Monocytes09:13

Isolation, Transfection, and Culture of Primary Human Monocytes

Published on: December 16, 2019

Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs18:46

Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs

Published on: December 9, 2010

Related Concept Videos

Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
Antiviral Nucleoside Inhibitors01:22

Antiviral Nucleoside Inhibitors

Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...