Abstract
The Gag polyprotein is the main retroviral structural protein and is essential for the assembly and release of virus particles. In this study, we have analyzed the morphology and Gag stoichiometry of human T-cell leukemia virus type 1 (HTLV-1)-like particles and authentic, mature HTLV-1 particles by using cryogenic transmission electron microscopy (cryo-TEM) and scanning transmission electron microscopy (STEM). HTLV-1-like particles mimicked the morphology of immature authentic HTLV-1 virions. Importantly, we have observed for the first time that the morphology of these virus-like particles (VLPs) has the unique local feature of a flat Gag lattice that does not follow the curvature of the viral membrane, resulting in an enlarged distance between the Gag lattice and the viral membrane. Other morphological features that have been previously observed with other retroviruses include: (1) a Gag lattice with multiple discontinuities; (2) membrane regions associated with the Gag lattice that exhibited a string of bead-like densities at the inner leaflet; and (3) an arrangement of the Gag lattice resembling a railroad track. Measurement of the average size and mass of VLPs and authentic HTLV-1 particles suggested a consistent range of size and Gag copy numbers in these two groups of particles. The unique local flat Gag lattice morphological feature observed suggests that HTLV-1 Gag could be arranged in a lattice structure that is distinct from that of other retroviruses characterized to date.
Highlights
10–20 million people are infected with human T-cell leukemia virus type 1(HTLV-1) worldwide [1,2]
A comparative analysis of HTLV-1-like particles and authentic, mature HTLV-1 particles was performed by cryogenic transmission electron microscopy and scanning transmission electron microscopy (STEM). These findings provide the first demonstration of the morphology of these virus-like particles (VLPs) having the unique feature of local flat Gag lattice regions that did not follow the curvature of the viral membrane and had an enlarged distance toward the membrane
HTLV-1-like particles produced using the HTLV-1 Gag-only expression construct (Figure 1A) were observed to be spherical in shape with a mean diameter of 110 ̆ 32 nm measured from 1172 particles (Figure 1B,C). This is in contrast to a previous study using a Gag-yellow fluorescence protein (YFP) expression construct in which a mean particle diameter of 71 ̆ 20 nm was determined by cryo-TEM [21]
Summary
10–20 million people are infected with human T-cell leukemia virus type 1(HTLV-1) worldwide [1,2]. HTLV-1 is a deltaretrovirus and is associated with adult T-cell leukemia/. Lymphoma, tropical spastic paraparesis, as well as HTLV-1-associated myelopathy [3,4]. These diseases are prevalent in places highly endemic for HTLV-1 infection such as southwestern Japan, central Africa, South America and the Caribbean. Despite the association of HTLV-1 with cancer and its significant impact on human health and well-being, the molecular mechanisms of viral replication, virus particle assembly and morphology remain poorly understood due to difficulties in propagating the virus in tissue culture. The assembly and budding of HTLV-1 particles is directed by the viral Gag polyprotein (recently reviewed by Maldonado et al [5]). HTLV-1 Gag molecules translocate to Viruses 2016, 8, 132; doi:10.3390/v8050132 www.mdpi.com/journal/viruses
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
