HIV Interaction and Viral Evolution Center Resources

CellVIEW

HIV in CellPack - reduced

CellVIEW is a new tool that provides fast rendering of very large biological macromolecular scenes and is inspired by state-of-the-art computer graphics techniques. CellVIEW is implemented in a free-to-use game engine, unity3D. CellVIEW provides fast rendering by introducing new means to efficiently reduce the amount of processed geometries. CellVIEW is unique and has been specifically designed to match the ambitions of structural biologist to model and interactively visualize structures comprised of several billions atoms, such as this model of an entire HIV virion in blood plasma. CellVIEW is the fruit of a collaboration with Mathieu Le Muzic and Ivan Viola from the Vienna University of Technology. The software is free for download at http://www.autopack.org/home/cellview

Visualization of HIV



These illustrations attempt to depict HIV based on currently available structural and biochemical information. We are interested in updating the images as new information becomes available. Please feel free to leave comments and critiques using the comment box at the bottom of the page, or by contacting me directly at goodsell@scripps.edu .

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Mature HIV 2016ALLINI-inhibited HIV 2016

Mature and ALLINI-Inhibited HIV (David S. Goodsell 2016)

Recent results from HIVE Center researchers have revealed that integrase is important for packaging the HIV genome inside the capsid, and that ALLINIs aggregate integrase and often lead to virions with the genome outside the capsid. These two paintings show cross sections of mature HIV (left) and HIV inhibited with ALLINIs (right).

See Kessl et al. "HIV-1 integrase binds the viral RNA genome and is essential during virion morphogenesis" Cell 166, 1257-1268.

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Cross section of immature HIV (2013, David S. Goodsell)

This painting depicts the immature HIV particle, after budding but before maturation. Gag is in light pink, other viral protein is in magenta, RNA is in yellow, cellular protein is in blue and tRNA is in green.

Click here for a description of the scientific references used for the illustration.

Click on the image for a full-size file.

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Cross section of mature HIV (2011, David S. Goodsell)

This painting depicts the mature HIV particle, with structural proteins in blue, viral enzymes in magenta, accessory proteins in green and viral RNA in yellow. Host proteins and tRNA are shown in purple.

Several educational resources are available at the Protein Data Bank, using this image in an interactive Flash activity and a poster.

The science behind the painting is described in: BAMBED 40, 291-296 (2012)

Click on the image for a full-size version.

HIV Life Cycle



HIV Life Cycle (2015, David S. Goodsell)

These illustrations integrate information from structural biology, electron microscopy, and biophysical studies, with goal of simulating a view of the macromolecular structure of HIV in its cellular environment. Each illustration captures the virus at one point in its life cycle, in a cross section that shows all macromolecules and membranes. Current efforts are extending these semiquantitative illustrations, using these diverse sources of information to specify 3D models of HIV and its interaction with host cells, for use in hypothesis generation and simulation.

1 - HIV and Antibodies
In this cross section, HIV is shown at lower right, with viral proteins in red and magenta, and viral RNA in yellow. Blood plasma is shown at the top and left side. Several broadly-neutralizing antibodies (A) are binding to HIV envelope glycoprotein (B). Other viral proteins include matrix (C), capsid (D), reverse transcriptase (E), integrase (F), protease (G), Vif (H) and Tat (I).



2 - HIV Attachment
In this cross section, HIV is shown at the top and a target cell is shown at the bottom in blues. HIV envelope protein (A) has bound to the receptor CD4 (B) and then to coreceptor CCR5 (C), causing a change in conformation that inserts fusion peptides into the cellular membrane.



3 - HIV Reverse Transcription and Nucleocapsid
After the capsid has entered the cell, reverse transcriptase (A) creates a DNA copy (green) of the HIV RNA genome (yellow), using a cellular transfer RNA (B) as primer. HIV nucleocapsid protein (C) acts as a chaperone to unfold the RNA secondary structure. The ribonuclease activity of RT removes the viral RNA after the DNA strand is created. Interaction of HIV Vif (D) with cellular APOBEC (E) is also shown.



4 - HIV Integration
Uncoating of the viral capsid (shown at the top) and interaction with nuclear pore proteins such as Nup358 (A) releases the viral DNA (B). The DNA enters the nucleus through the nuclear pore (shown in purple) and is spliced into the cellular genome by the enzyme HIV integrase (C). Cellular protein LEDGF (D) is important for localization of the site of integration at DNA in nucleosomes (E).



5 - HIV Transcription and Tat Protein
HIV Tat protein (A), bound to the TAR RNA stem-loop structure, binds to the P-TEFb complex (B), activating transcriptional elongation by RNA polymerase (C). The illustration also shows HIV Rev (D) bound to the Rev-response element and CRM1 (E), a cellular protein involved in transport through the nuclear pore.



6 - HIV Translation
The HIV gag polyprotein (A, shown in red) is translated from the HIV RNA genome (in yellow) by cellular ribosomes (B). A stem-loop structure in the genome (C) induces a frame shift roughly 5% of the time, producing the longer gag-pol protein (D).



7 - HIV Budding
HIV gag protein (A) and gag-pol (B) form arrays on the cell surface, capturing two copies of HIV genome (in yellow), which dimerize through a specific sequence (C) and bind to a cellular transfer RNA (D) that will act as primer for reverse transcription. Viral proteins Vpr (E) and Vif (F) are also incorporated. Several cellular proteins of the ESCRT system (G) are involved in the process of budding.



8 - HIV Maturation
This illustration shows an immature viron in the process of maturation at bottom right and a nearly-mature virion at upper left. HIV protease (A) is cleaving the gag and gag-pol proteins into functional proteins.

Online Resources





Links to online resources about HIV structure and function

Science of HIV at the CHEETAH Center

Science of HIV

faah

FightAIDS@Home uses your computer's idle cycles to assist fundamental research in discovering new drugs, building on our growing knowledge of the structural biology of AIDS.

Specialized Centers for HIV/AIDS-related Structural Biology

Five Centers are currently supported by the AIDS-Related Structural Biology Program at NIGMS:

Center for RNA Studies (CRNA), Alice Telesnitsky, PI

Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking and Assembly of HIV (CHEETAH), Wesley Sundquist, PI

HIV Accessory and Regulatory Complexes (HARC) Center, Alan Frankel, PI

Pittsburgh Center for HIV Protein Interactions, Angela Gronenborn, PI

HIV Interaction and Viral Evolution (HIVE) Center, Arthur Olson, PI

Databases

RCSB Protein Data Bank

HIV Drug Resistance Database