The first strains of human immunodeficiency virus appeared in the early XX century in Africa (34). The closest evolutionary ancestors of HIV viruses were similar to simian immunodeficiency viruses, and the first infected humans could be hunters who butchered the dead monkeys. Currently, according to the World Health Organization, nearly 37 million people worldwide are HIV-infected, and the immunodeficiency caused by the virus killed more than a million people in 2015 (35).
The human immunodeficiency virus (HIV) is a retrovirus and a member of the lentivirus genus. HIV infects and destroys cells of the human immune system (CD4+ T-lymphocytes, macrophages and dendritic cells).The decrease in CD4+ T-lymphocyte levels causes the development of acquired immunodeficiency syndrome (AIDS) (36).
There are two major species of HIV, HIV-1 and HIV-2, of which HIV-2 is less common. The HIV virion is a roughly spherical particle with a diameter measuring between 100 and 180 nm. The virion is surrounded by a cell-derived lipid membrane, which contains surface proteins. Some of these membrane proteins are products of the viral genome (surface glycoprotein gp120/gp41), and others are captured from the host cell during viral budding (e.g., ICAM-1, HLA-DR1, CD55 and others). The gp120/gp41 glycoprotein interacts with receptors on the cell surface promoting fusion of the viral and cell membranes. Other HIV surface proteins perform supporting functions (4, 6).
Trimers of the MA (p17) protein form a layer directly under the lipid membrane. Inside the HIV particle is a cone-shaped capsid, which is composed of CA (p24) proteins. The capsid contains two copies of positive single-stranded viral RNA bound by the NC (p7) protein and the enzymes (reverse transcriptase and integrase) necessary for replication of the virus (15, 37).
The HIV genome is approximately 10,000 nucleotides in length and contains 9 genes encoding 15 different proteins. The most important viral genes (open reading frames) are Gag, Pol and Env. Gag encodes the p55 protein, which is subsequently cut into the structural proteins MA, CA, NC and p6. The Pol reading frame encodes integrase, protease, and reverse transcriptase. Env encodes the two subunits of the surface glycoprotein complex. Other genes (Tat, Rev, Vif, Vpr, Vpu and Nef) produce accessory proteins, which modulate host cell metabolism and facilitate different stages of the HIV life cycle (38).
This human immunodeficiency virus model summarizes the results from more than 100 of the latest scientific publications in the fields of virology, X-ray analysis and NMR spectroscopy. The depicted spatial configurations of 17 different viral and cellular proteins found in the HIV particle are in strict accordance with known 3D structures.The viral membrane in the model includes 160,000 lipid molecules of 8 different types in the proportion found in the HIV particle.
Scientifically verifying accurate models of viruses remains a challenging task. This becomes more complicated due to the fact that none of the currently available scientific approaches allow for obtaining an image of the whole virus particle in the atomic or molecular resolution. Nevertheless, hundreds of works by different authors from around the world have shed light on the structure and morphology of virion components and their interactions. The Visual Science team relies on several important sources to create models of the non-profit educational project “Viral Park”: careful analysis of the available scientific publications; opinions of recognized experts from the world's top research centers and the results of our own molecular dynamics and modeling simulations made by the experts of Visual Science’s Molecular modeling department, who employ structural bioinformatics methods to fill the gaps in the current understanding of the viral structure.This model of the HIV virion has been awarded the first place at the 2010 Science and Engineering Visualization Challenge (SEVC), a competition organized by Science magazine and the National Science Foundation.
The model appeared on the cover of the special issue of Nature Medicine (September 8, 2010) prepared by the Global HIV Vaccine Enterprise. In this publication, the Enterprise published the strategic research plan to accelerate the development of vaccines against HIV (the “2010 Plan”). The 2010 Plan was developed by the Council of the Global HIV Vaccine Enterprise with the participation of hundreds of scientists, policy-makers, funders, and advocates worldwide.
The model also appeared on the cover of the International AIDS Vaccine Initiative (IAVI) Report. It is an authoritative guide that publishes information about all events and innovations, concerning the development of the vaccine against HIV. The IAVI report is published 6 times a year and its audience is represented by specialists in more than 130 countries. The mission of the InternationalAIDS Vaccine Initiative is to ensure the development of safe, effective, accessible, preventive HIV vaccines for use throughout the world. IAVI participates in research and development of candidate vaccines, addressing the legal issues concerning HIV and AIDS, supporting developing countries. The IAVI Innovation Fund is supported by the Bill and Melinda Gates Foundation. IAVI has representative offices in Africa, Europe, India, and the US.
In addition, our HIV model has been included in Stanley Plotkin's Vaccines, a textbook hailed as the “Bible of vaccinologists” by The Lancet; featured in presentations by the Nobel Prize-winning virologist Françoise Barré-Sinoussi; and covered by The New York Times, National Geographic, Wired, Popular Science, and other popular periodicals.
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