Viruses in the Nucleus

Abstract

Viral infection is intrinsically linked to the capacity of the virus to generate progeny. Many DNA and some RNA viruses need to access the nuclear machinery and therefore transverse the nuclear envelope barrier through the nuclear pore complex. Viral genomes then become chromatinized either in their episomal form or upon integration into the host genome. Interactions with host DNA, transcription factors or nuclear bodies mediate their replication. Often interfering with nuclear functions, viruses use nuclear architecture to ensure persistent infections. Discovering these multiple modes of replication and persistence served in unraveling many important nuclear processes, such as nuclear trafficking, transcription, and splicing. Here, by using examples of DNA and RNA viral families, we portray the nucleus with the virus inside.

Figure 1.

Viral nuclear entry. Influenza viral RNA enters the nuclei aided by importins while adeno-/herpesviruses attach to the nuclear pore complex (NPC) for the release of the genomic material. The lentivirus, HIV-1, travels with the capsid (CA). (Inset) 3D rendering of electron tomographic reconstruction showing the HIV-1 CA mutant A77 V (CPSF6-binding deficient) entering the NPC central channel in infected T lymphoblast SupT1-R5. (NE) Nuclear envelope, (MTs) microtubules. (Image kindly provided by Dr. Vojtech Zila and Erica Margiotta.)

Figure 2.

Integration of HIV-1 provirus favors active A compartments. (Upper panel) Cluster of genes recurrently targeted by HIV-1. Triple-color fluorescence in situ hybridization (FISH) of GRB2 (magenta), RNF157 (red), and TNRC6C (green) in resting and activated CD4⁺ T cells. Maximum projections for each of the channels and merge images are shown. Nuclei were counterstained with Hoechst 33342 (blue). Scale bar, 4 μm. (Lower panel) Distribution of recurrent integration genes (RIGs) (bold) and single HIV-1 integration sites (plain) at the chromosomal region 17q25.1-3 within 20 Mb. Genes analyzed by triple-color FISH are depicted in magenta, red, and green. Distances between them on the linear DNA are indicated. (Images made by the Lusic laboratory in collaboration with V. Roukoss.)

Figure 3.

Interaction of viral genetic material with nuclear bodies (NBs). (Left panel) Human cytomegalovirus (HCMV)-infected cell triple-labeled with ND10 (promyelocytic [PML]) in red, IE transcripts in green, and SC35 in blue. Transcript signals appear to locate with the highest concentration at ND10 and are also found in the SC35 domain. (Inset) Arrangement as expected when all three components colocalize. (Inset preprinted from Ishov et al. 1997 with permission from Rockefeller University Press © 1997.) (Right panel) Images show HIV-1 DNA fluorescence in situ hybridization (FISH) (red) associated with promyelocytic (PML) nuclear bodies (NBs) (scale bar, 2 μm), (green) in latent cells and HIV-1 transcripts, RNA FISH (red) in activated cells where no PML NBs are detected. (Right panel from Shytaj et al. 2020; reprinted, with permission, from the authors in conjunction with the terms of the Creative Commons BY 4.0 license.)