Abstract
The efficiency of reverse transcription to synthesize viral DNA in infected cells greatly influences replication kinetics of retroviruses. However, viral replication in non-dividing cells such as resting T cells and terminally differentiated macrophages is potently and kinetically restricted by a host antiviral factor designated SAMHD1 (sterile alpha motif and HD-domain containing protein 1). SAMHD1 reduces cellular deoxynucleoside triphosphate (dNTP) pools and affects viral reverse transcription step. Human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency viruses (SIVs) have Vpx or Vpr to efficiently degrade SAMHD1. Interestingly, the reverse transcriptase (RT) derived from HIV-1 that encodes no anti-SAMHD1 proteins has been previously demonstrated to uniquely exhibit a high enzymatic activity. It is thus not irrational to assume that some viruses may have acquired or lost the specific RT property to better adapt themselves to the low dNTP environments confronted in non-dividing cells. This adaptation process may probably be correlated with the SAMHD1-antagonizing ability by viruses. In this report, we asked whether such adaptive events can be inferable from Vpx/Vpr and RT phylogenetic trees overlaid with SAMHD1-degrading capacity of Vpx/Vpr and with kinetic characteristics of RT. Resultant two trees showed substantially similar clustering patterns, and therefore suggested that the properties of RT and Vpx/Vpr can be linked. In other words, HIV/SIVs may possess their own RT proteins to adequately react to various dNTP circumstances in target cells.
Highlights
Accessory proteins of various human immunodeficiency viruses/simian immunodeficiency viruses (HIV/SIVs) are believed to be essential for optimal viral replication, persistence, and pathogenicity in vivo (Matheson et al, 2016)
Phylogenetic Insights into RT and Vpx/Vpr findings to understand the interaction of Vpx and SAMHD1 (Goldstone et al, 2011; Hrecka et al, 2011; Laguette et al, 2011, 2012; Baldauf et al, 2012; Descours et al, 2012; Lahouassa et al, 2012; Lim et al, 2012; St Gelais et al, 2012; Lenzi et al, 2014, 2015): (1) all Vpx and some Vpr proteins derived from various HIV/SIVs target SAMHD1 for proteasomal degradation; (2) SAMHD1 reduces cellular deoxynucleoside triphosphate pools to a level similar to that observed in non-dividing myeloid and resting T cells; (3) HIV-1 reverse transcriptase (RT) shows a high binding affinity to dNTPs relative to those from other lentiviruses
In order to see the genetic background for the results described above (Laguette et al, 2012; Lim et al, 2012), we inferred a bootstrap phylogenetic tree of Vpx/Vpr proteins from diverse HIV/SIVs by the neighbor-joining method as previously described (Sakai et al, 2016), and the proteins with/without SAMHD1-degrading activity were highlighted by blue and red letters, respectively
Summary
Accessory proteins of various human immunodeficiency viruses/simian immunodeficiency viruses (HIV/SIVs) are believed to be essential for optimal viral replication, persistence, and pathogenicity in vivo (Matheson et al, 2016). Vpx was least well studied among the five accessory proteins (Vif, Vpx, Vpr, Vpu, and Nef) for its functional role and the underlying molecular basis until the recent identification of cellular anti-viral factor SAMHD1 as a target for Vpx (Hrecka et al, 2011; Laguette et al, 2011).
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