Lambda interferon inhibits human immunodeficiency virus type 1 infection of macrophages

Wei Hou1, Xu Wang, Li Ye

  • 1Division of Allergy & Immunology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104, USA.

Journal of Virology
|February 6, 2009
PubMed

Insights

Type III interferon (IFN-lambda) inhibits human immunodeficiency virus type 1 (HIV-1) replication in macrophages. This antiviral activity involves both extracellular and intracellular mechanisms, suggesting therapeutic potential for HIV-1 infection.

Area of Science:

  • Immunology
  • Virology
  • Infectious Diseases

Background:

  • Type III interferon (IFN-lambda) is a newly identified cytokine with broad-spectrum antiviral activity.
  • Human immunodeficiency virus type 1 (HIV-1) infects macrophages, a critical cell type in viral replication and pathogenesis.
  • Understanding novel antiviral mechanisms is crucial for developing effective HIV-1 therapies.

Purpose of the Study:

  • To investigate the antiviral potential of type III interferon (IFN-lambda) against human immunodeficiency virus type 1 (HIV-1) in macrophages.
  • To elucidate the mechanisms by which IFN-lambda inhibits HIV-1 infection and replication.

Main Methods:

  • Blood monocyte-derived macrophages expressing IFN-lambda receptors were cultured.
  • Macrophages were treated with IFN-lambda1 or IFN-lambda2 and subsequently infected with HIV-1.
  • HIV-1 infection, replication, CCR5 expression, CC chemokine induction, and intracellular APOBEC3G/3F expression were analyzed.

Main Results:

  • IFN-lambda1 and IFN-lambda2 significantly inhibited HIV-1 infection and replication in macrophages.
  • The antiviral effect was observed against both laboratory-adapted and clinical HIV-1 strains.
  • IFN-lambda induced CC chemokines and upregulated intracellular APOBEC3G/3F, while having minimal effect on CCR5 expression.

Conclusions:

  • Type III interferon (IFN-lambda) possesses broad-spectrum anti-HIV-1 activity in macrophages.
  • IFN-lambda inhibits HIV-1 replication through both extracellular (chemokine induction) and intracellular (APOBEC3G/3F upregulation) antiviral mechanisms.
  • These findings highlight the therapeutic potential of IFN-lambda for treating HIV-1 infection.

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...
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
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...