Abstract
Since its discovery in the early 1980s, there has been significant progress in understanding the biology of type 1 human immunodeficiency virus (HIV-1). Structural biologists have made tremendous contributions to this challenge, guiding the development of current therapeutic strategies. Despite our efforts, there are unresolved structural features of the virus and consequently, significant knowledge gaps in our understanding. The superstructure of the HIV-1 matrix (MA) shell has not been elucidated. Evidence by various high-resolution microscopy techniques support a model composed of MA trimers arranged in a hexameric configuration consisting of 6 MA trimers forming a hexagon. In this manuscript we review the mathematical limitations of this model and propose a new model consisting of a 6-lune hosohedra structure, which aligns with available structural evidence. We used geometric and rotational matrix computation methods to construct our model and predict a new mechanism for viral entry that explains the increase in particle size observed during CD4 receptor engagement and the most common HIV-1 ellipsoidal shapes observed in cryo-EM tomograms. A better understanding of the HIV-1 MA shell structure is a key step towards better models for viral assembly, maturation and entry. Our new model will facilitate efforts to improve understanding of the biology of HIV-1.
Highlights
Over the last few decades, the scientific community has reported tremendous structural heterogeneity in type 1 human immunodeficiency virus (HIV-1), involving factors such as number of cores per particle, shape of the capsid cores and virion size
Given the limitations of the existing structural models for HIV, we developed a novel model for the HIV-1 MA shell and used this model to predict the number of MA protein units needed to assemble mature virions for the full range of observed HIV-1 particle diameters (100–200 nm)
Understanding the various structural characteristics of the pathogen is a powerful guide in our efforts to understand the pathophysiology of HIV-1
Summary
Over the last few decades, the scientific community has reported tremendous structural heterogeneity in type 1 human immunodeficiency virus (HIV-1), involving factors such as number of cores per particle, shape of the capsid cores and virion size. This structural diversity was documented by Johnson et al, in their efforts to develop a structurally accurate mesoscale model of HIV-1 [1]. Given the unique nature of individual virions, development of a consensus model for HIV-1 is unlikely. As we increase our general understanding of structural irregularities, a more refined model will shed light upon unresolved mechanisms in viral particle formation, maturation and viral entry.
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