HIV-1 buds predominantly at the plasma membrane of primary human macrophages

Sonja Welsch1, Oliver T Keppler, Anja Habermann

  • 1Department of Virology, University of Heidelberg, Heidelberg, Germany.

Plos Pathogens
|March 27, 2007
PubMed

Insights

Contrary to popular belief, Human Immunodeficiency Virus type 1 (HIV-1) primarily buds from the plasma membrane, not late endosomes, in macrophages. This study used a novel ultrastructural method to reveal this key finding about HIV-1 assembly and release.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • HIV-1 assembly and release typically occur at the plasma membrane.
  • Previous studies suggested exclusive HIV-1 budding at late endosomes in primary macrophages.
  • This discrepancy highlights a gap in understanding HIV-1 egress mechanisms in different cell types.

Purpose of the Study:

  • To investigate the precise site of HIV-1 assembly and release in primary macrophages.
  • To challenge the existing paradigm of HIV-1 budding occurring exclusively at late endosomes in macrophages.
  • To utilize a novel ultrastructural approach for immunomarker-independent analysis of HIV-1 budding.

Main Methods:

  • Employed a novel ultrastructural technique in primary macrophages infected with HIV-1.
  • Utilized BSA-gold to label endosomes and ruthenium red to stain the plasma membrane.
  • Analyzed virus-filled vacuolar structures for the presence of BSA-gold and ruthenium red staining.
  • Examined the composition of cellular marker proteins within the HIV-1 envelope.

Main Results:

  • Virus-containing vacuoles showed ruthenium red staining (indicating plasma membrane) but lacked BSA-gold (indicating not endosomes).
  • HIV-1 budding profiles were rarely found on gold-labeled endosomes.
  • HIV-1 budding was frequently observed on ruthenium red-positive membranes.
  • Analysis of incorporated cellular proteins supported a plasma membrane origin for the viral envelope.

Conclusions:

  • The plasma membrane is the primary site of HIV-1 budding in primary macrophages.
  • This finding contradicts the prevailing view of exclusive late endosomal budding in these cells.
  • The study provides crucial insights into the cell biology of HIV-1 replication and release.

Related Concept Videos

Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
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...
Size and Structure of Viral Genomes01:26

Size and Structure of Viral Genomes

Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...