Adenovirus-induced leakage of co-endocytosed macromolecules into the cytosol

Insights

Adenovirus enhances the uptake of macromolecules like fluorescein isothiocyanate-labeled dextran into KB cells. This increased uptake and viral entry depend on passage through an acidic cellular compartment.

Area of Science:

  • Cell Biology
  • Virology

Background:

  • Adenovirus interaction with host cells is crucial for viral infection.
  • Understanding early viral entry mechanisms is key to developing antiviral strategies.

Purpose of the Study:

  • To investigate the early interaction between KB cells and adenovirus.
  • To elucidate the role of acidic compartments in adenovirus entry and macromolecule uptake.

Main Methods:

  • Utilized KB cells and adenovirus.
  • Measured uptake of fluorescein isothiocyanate-labeled dextran (FD) using fluorescence microscopy.
  • Assessed the effect of pH-altering drugs (chloroquine, ammonium chloride, monensin) on FD uptake and viral entry.

Main Results:

  • Adenovirus significantly increased cell-associated FD uptake (2-3 fold) compared to controls.
  • Cells incubated with adenovirus showed widespread fluorescence, unlike control cells with localized vesicle fluorescence.
  • Inhibition of acidic compartments with drugs blocked both increased FD uptake and adenovirus nuclear entry.

Conclusions:

  • Adenovirus entry into KB cells involves passage through an acidic compartment, likely endocytic vesicles.
  • Co-endocytosed macromolecules are released into the cytosol upon viral entry.
  • The findings suggest a pH-dependent mechanism for adenovirus cellular entry.

Related Concept Videos

Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview
Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
Vesicular Tubular Clusters01:45

Vesicular Tubular Clusters

After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
Coronavirus01:29

Coronavirus

Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), are enveloped viruses characterized by their single-stranded, positive-sense RNA genome and helical nucleocapsid structure. The hallmark of these viruses is their club-shaped spike (S) glycoproteins that protrude from the viral envelope, facilitating attachment to host cells. Typically, coronaviruses infect the upper respiratory tract, often causing mild or asymptomatic disease. However, certain strains like...
Respiratory Syncytial Virus Disease01:29

Respiratory Syncytial Virus Disease

Human respiratory syncytial virus (RSV) is a widespread pathogen that primarily targets infants and young children but also poses a serious health risk to elderly and immunocompromised individuals. Belonging to the Pneumoviridae family, RSV is a negative-sense, single-stranded RNA virus within the Pneumovirus genus. Its global health burden is significant, with millions of cases annually resulting in hospitalizations and mortality, particularly in resource-limited settings. Although most...