Cellular processes essential for African swine fever virus to infect and replicate in primary macrophages

Sameh Basta1, Heidi Gerber, Alexander Schaub

  • 1Department of Microbiology and Immunology, Queen's University, Kingston, ON, Canada. bastas@queensu.ca

Insights

African swine fever virus (ASFV) infects macrophages through multiple entry routes, not just receptor-mediated endocytosis. The virus utilizes specific cellular processes for replication, avoiding lysosomal degradation while depending on certain lysosomal functions.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Macrophages (Mø) are crucial innate immune cells targeted by African swine fever virus (ASFV).
  • Previous ASFV infection studies focused on non-leukocyte cells like Vero cells.
  • Understanding ASFV's interaction with primary macrophages is essential for controlling swine fever.

Purpose of the Study:

  • To characterize key parameters of ASFV infection in primary macrophages.
  • To elucidate the entry mechanisms and intracellular processing of ASFV in Mø.
  • To identify cellular processes vital for ASFV replication within macrophages.

Main Methods:

  • Investigated ASFV entry into primary macrophages, assessing receptor-mediated endocytosis and alternative pathways.
  • Analyzed the roles of divalent cations, microtubule assembly, and actin-dependent processes in viral entry and trafficking.
  • Examined ASFV's interaction with lysosomes and autophagosomes, evaluating the impact of specific inhibitors on viral replication.

Main Results:

  • ASFV entry into macrophages is not solely receptor-mediated endocytosis; phagocytosis is also implicated.
  • Divalent cations and microtubule assembly are critical for ASFV endocytic and endosomal processing.
  • ASFV circumvents mature lysosome degradation but requires specific propylamine-sensitive lysosomal functions for replication.

Conclusions:

  • ASFV employs diverse cellular mechanisms for entry and replication in macrophages.
  • The virus strategically manipulates host cell machinery, including endocytic pathways and lysosomal functions.
  • These findings enhance understanding of viral pathogenesis in immune scavenger cells, aiding in disease control strategies.

Related Concept Videos

Intracellular Movement of Viruses and Bacteria01:10

Intracellular Movement of Viruses and Bacteria

Intracellular bacteria and viruses often comprise a group of highly infectious pathogens that can cause several diseases. Bacterial pathogens include those belonging to the genus Rickettsia responsible for conditions such as rocky mountain spotted fever and the Mediterranean spotted fever; Chlamydia, a genus responsible for a sexually transmitted disease; Coxiella burnetii, an agent responsible for Q fever. Viral pathogens include vaccinia—a poxvirus, and herpes simplex virus—a virus that...
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...
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 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...
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview