Abstract
Integration of retroviral reverse transcripts into the chromosomes of the cells that they infect is required for efficient viral gene expression and the inheritance of viral genomes to daughter cells. Before integration can occur, retroviral reverse transcription complexes (RTCs) must access the nuclear environment where the chromosomes reside. Retroviral integration is non-random, with different types of virus-host interactions impacting where in the host chromatin integration takes place. Lentiviruses such as HIV efficiently infect interphase cells because their RTCs have evolved to usurp cellular nuclear import transport mechanisms, and research over the past decade has revealed specific interactions between the HIV capsid protein and nucleoporin (Nup) proteins such as Nup358 and Nup153. The interaction of HIV capsid with cleavage and polyadenylation specificity factor 6 (CPSF6), which is a component of the cellular cleavage and polyadenylation complex, helps to dictate nuclear import as well as post-nuclear RTC invasion. In the absence of the capsid-CPSF6 interaction, RTCs are precluded from reaching nuclear speckles and gene-rich regions of chromatin known as speckle-associated domains, and instead mis-target lamina-associated domains out at the nuclear periphery. Highlighting this area of research, small molecules that inhibit capsid-host interactions important for integration site targeting are highly potent antiviral compounds.
Highlights
Viruses 2021, 13, 125. https://Retroviruses are the only type of animal virus that routinely recombine their genetic information with that of the infected host organism
HIV-1 gained significant preference to integrate into lamina-associated domains domains (LADs) [15], heterochromatin domains that physically associate with nuclear lamina (Figure 1) [16]
Recent results have highlighted that HIV-1 reverse transcription complexes (RTCs)/preintegration complex (PIC) congregate at nuclear speckles in a CPSF6dependent manner [12,114] for integration into speckle-associated domains (SPADs) [12]
Summary
Retroviruses are the only type of animal virus that routinely recombine their genetic information with that of the infected host organism. The nucleoprotein complex within the HIV-1 virion particle consists of two copies of plus-stranded genomic RNA bound by the viral nucleocapsid (NC) protein and reverse transcriptase (RT) and IN enzymes. The virion particle undergoes a series of transitional changes as it moves from the extracellular environment through the cell to reach the chromosomal DNA targets of integration within the nucleus. RT converts the two copies of HIV-1 RNA into one double-stranded DNA molecule within the confines of the reverse transcription complex (RTC), which in essence is the reverse transcription-competent viral core [1,2,3] (Figure 1). Retroviral reverse transcripts are integrated into host cell genomes in non-random fashions (reviewed in [9]).
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