SGM Journals

Research explained · Viral protein localization

How does dengue’s capsid protein get into a cell’s nucleus?

A stretch of amino acids in the dengue capsid protein helped it reach the nucleus in lab-grown cells. When the team removed that stretch, the protein stayed in the cytoplasm. Adding the stretch to a protein that normally stays in the cytoplasm sent that protein to the nucleus. [1]

See original studies View the SGM research record

How the team tested a possible targeting signal

Track the protein
In infected cells, an antibody detected core protein first in the cytoplasm and later in nuclei and nucleoli.
The protein reached the nucleolus, a structure within the nucleus, later in the experiment. [1]
Remove candidate signals
Changing the first two candidates still allowed the protein to reach the nucleus. Removing the two-part signal at amino acids 85 to 100 kept the protein out of the nucleus in the tested construct.
That stretch was necessary for nuclear localization in this part of the experiment. [1]
Transfer the signal
The two-part motif also directed a normally cytoplasmic protein to the nucleus.
The signal also worked when the researchers attached it to another protein. [1]

What is a nuclear localization signal?

A nuclear localization signal is a short stretch of amino acids that helps a protein reach the nucleus. The dengue segment had two groups of amino acids separated by a gap, so the researchers called it a bipartite signal. [1]

Did the protein need the rest of the virus to get there?

The researchers gave cells the gene for the capsid protein by itself and still detected the protein in nuclei and nucleoli. Other dengue proteins were unnecessary for the targeting seen in those cells. [1]

What do we know about what the protein does there?

The localization experiment followed the capsid protein. It did not track where the viral RNA replicates. Later experiments found that the capsid interacts with a host protein called nucleolin and reported a role for nucleolin in making infectious particles. The effect of the capsid’s nuclear location on infection remained a separate question. [1][2]

Original research

  1. Wang et al. (2002), Journal of General Virology. Intracellular localization and determination of a nuclear localization signal of the core protein of dengue virus. Primary immunofluorescence, motif deletion and transfer experiments.
  2. Balinsky et al. (2013), Journal of Virology. Nucleolin interacts with the dengue virus capsid protein and plays a role in formation of infectious virus particles. Later functional work on a capsid interaction with a host protein.