http://www.sciencecodex.com/read/nih_scientis...workings_of_viruses-84306

[...] a new way to see structures within viruses that were not clearly seen before [...] Cryo-electron microscopy (cryo-EM) is a technique that allows scientists to image very small particles, like structures on the surface of viruses. [...] "We first used low doses of radiation and recorded images in which the inner structure of the virus was invisible," said Steven. "Next, we used high doses of radiation, and found that the inner structure could be seen as a cylinder of bubbles." While the inner structure was damaged, the team was able to superimpose the images, using three-dimensional computer reconstruction. As a result, they were able to clearly visualize the viral structure. The investigators call this technique bubblegram imaging. [...] this technique will allow a better understanding of the inner workings of viruses, providing more opportunities for developing novel therapies. Beyond studying viral structure, cryo-EM could be used to visualize interactions of proteins with DNA in human cells. One exciting prospect lies in using this approach to visualize differences in cancer vs. non-cancer cells. "This new cryo-EM procedure renders previously invisible proteins visible and, thus, will provide new understanding of cell biology," [...]

"... As announced in Rome, the IAS is developing a global scientific campaign called Towards an HIV Cure. This campaign will be launched at the "XIX International AIDS Conference," which will take place in Washington, D.C., USA, in July 2012. The main objective of the campaign is to develop a global consensus and define scientific priorities aimed at a finding a cure for HIV."

"...in the early 1990s, it was unthinkable to speak of a cure when not even one effective treatment was available."

"It happened suddenly, like how everything happens”. These were the last words of an article titled “The Day of the Cure” published in 1992 in a Brazilian newspaper, Jornal do Brasil (1). The article narrates how Herbert de Souza — a well-known Brazilian sociologist and activist, nicknamed Betinho — imagines the day when the cure for AIDS is announced.

http://www.hiv-reservoir.net/index.php/the-ne...ist-and-the-hiv-cure.html

http://www.eurekalert.org/pub_releases/2012-01/fhcr-ttb012412.php

"Public release date: 26-Jan-2012

Tracking the birth of an evolutionary arms race between HIV-like viruses and primate genomes

SEATTLE – Using a combination of evolutionary biology and virology, scientists at Fred Hutchinson Cancer Research Center have traced the birth of the ability of some HIV-related viruses to defeat a newly discovered cellular-defense system in primates.

The research, led by Michael Emerman, Ph.D., a member of the Hutchinson Center's Human Biology and Basic Sciences Division, and Harmit Malik, Ph.D., a member of the Center's Basic Sciences Division, was published online Jan. 26 ahead of the Feb. 16 print issue of Cell Host & Microbe.

The work, which also involved researchers in the Hutchinson Center's Computational Biology Program, hinges on the recently discovered cellular-defense protein called SAMHD1, which protects some key cells of the immune system from infection by HIV-1. The protein likely accomplishes this by reducing the available nucleotides, or DNA building blocks, the virus needs for replicating. In response, some viruses related to HIV-1, such as HIV-2 and some simian immunodeficiency viruses that infect other primates, produce a protein called Vpx that binds to SAMHD1 and targets it for destruction.

HIV-1, however, does not encode Vpx, but it does encode a related protein called Vpr. Emerman and colleagues tried to address the question of whether HIV-1 lost the ability to degrade SAMHD1 or whether this ability was gained only in the minority of lentiviruses that encode a Vpx protein.

To distinguish between these possibilities, the researchers tested both Vpx as well as the related Vpr proteins from a panel representing all currently known primate lentiviruses for their ability to bind and degrade SAMHD1. When the phylogenetic history, or evolutionary relatedness, between these two viral proteins was mapped on top of their functions, the researchers found that SAMHD1-degrading ability was acquired first by the Vpr protein before the Vpx protein was even "born."

This new function occurred only once, in a single evolutionary lineage representing three of eight currently known primate lentivirus types. "This means that the ability of lentiviruses to degrade primate SAMHD1 is a newly acquired trait," Emerman said. "However, HIV-1 does not have the capacity to degrade SAMHD1 because its Vpr gene derived from a lineage of viruses in primates that never evolved to gain this function."

The researchers also found that Vpr/Vpx proteins have highly species-specific abilities to degrade primate SAMHD1. Thus, while a lentivirus can degrade SAMHD1 within a single primate species, it cannot bind and degrade the SAMHD1 protein from a more distantly related species. The specificity of the virus for its particular host and the fact that SAMHD1 degradation was an evolutionary novelty among lentiviruses suggests that SAMHD1 from some primates is locked in an "evolutionary arms race" with Vpx/Vpr proteins.

Such genetic tugs of war exemplify what is known among evolutionary biologists as the Red Queen Principle, a phrase borrowed from the Red Queen in Lewis Carroll's "Through the Looking Glass" that refers to the paradox of running as fast as you can just to stay in place. "Red Queen conflicts" typically put pressure on both sparring partners to continually evolve new ways to outsmart and overcome each other just to stay in the game. In this case, the host proteins evolve to evade degradation by the newly evolved viral proteins.

To assess molecular signatures of these evolutionary arms races, first author Efrem Lim, a graduate student in Emerman's lab, compared the evolutionary rates of SAMHD1 across primate evolution. He found that prior to 23 million years ago, there was very little evidence for rapid evolution of SAMHD1. In contrast, SAMHD1 proteins in Old World monkeys that harbor Vpr/Vpx-containing lentiviruses have evolved rapidly for millions of years.

"We have not only recreated the birth of SAMHD1-degrading activity in these viruses but also have captured the immediate evolutionary consequence on the host genes they antagonize," said Malik, an evolutionary geneticist. "While such arms races between viruses and host genomes have been documented previously, this is the first instance where the beginning of the Darwinian arms race has been captured in both viral and primate genomes."

Emerman, a virologist, speculates the research may have direct implications for HIV-1 and AIDS. "It is possible that HIV-1 is so pathogenic because it needs to grow rapidly in order to compensate for the lack of the ability to deal with SAMHD1," he said."

No HIV-1 Reservoir Found in CD34+ Hematopotietic Progenitor Cells (HPCs)

"... if these results are confirmed, they will facilitate the work towards an HIV cure..."

http://www.hiv-reservoir.net/index.php/the-ne...ervoir-found-in-hpcs.html

http://www.sciencecodex.com/indiana_universit...s_protective_shield-85952

[...] It's not that the human immune system doesn't recognize HIV. Indeed, an infection causes the body to unleash antibodies that attack the virus, and initially some HIV is destroyed. But HIV is able to quickly defend itself by co-opting a part of the innate human immune system — the immune system people are born with, called the complement. The complement includes a vital mechanism that prevents immune system cells from attacking the body's own cells. HIV is able to incorporate a key protein in that self-protection mechanism, CD59, and by doing so makes itself appear to be one of the body's normal cells, not an infective agent. In laboratories at the Indiana University School of Medicine, Andy Qigui Yu, M.D., Ph.D., assistant professor of microbiology and immunology, is testing a promising compound that may counteract HIV's ability to hijack the immune system's protection mechanism. [...] The new grant will support not only Dr. Yu's research into compounds that may block the ability of HIV to hide behind the CD59 "cloak," but also his work to identify the mechanism the virus uses to incorporate CD59. "If we find that mechanism, then we can develop something to block that incorporation, and HIV may lose that protection from the immune system," Dr. Yu said. Researchers have been able in the past to generate antibodies that successfully attacked HIV in the laboratory. But these antibodies have failed in human testing because the virus in the body escapes from immune system attacks, Dr. Yu said. In an attempt to disrupt HIV's hijacking of CD59, Yu and colleagues at IU and Harvard University crafted a molecule from a bacterial toxin that is known to bind to the CD59 protein. In laboratory tests, they administered the molecule to blood samples taken from patients with HIV. The bacteria toxin molecule latched on to the CD59 proteins, revealing the viral particles to be invaders and enabling the antibodies to attack the virus. [...]