Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet (“airborne transmission”) between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets.
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The introduction of receptor-binding site mutations [...] in HA [hemagglutinin], acquired during ferret passage, did not result in increased cross-reactivity with human antisera [...], indicating that humans do not have antibodies against the HA of the airborne-transmissible A/H5N1 virus that was selected in our experiments.
Virologists have created H5N1 reassortants before. One study found that H5N1 did not produce transmissible hybrids when it reassorts with a flu strain called H3N24. But in 2011, Stacey Schultz-Cherry, a virologist at St. Jude Children's Research Hospital in Memphis, Tennessee, showed that pandemic H1N1 becomes more virulent if it carries the HA gene from H5N1. [...]
Chen’s team mixed and matched seven gene segments from H5N1 and H1N1 in every possible combination, to create 127 reassortant viruses, all with H5N1’s HA gene. Some of these hybrids could spread through the air between guinea pigs in adjacent cages, as long as they carried either or both of two genes from H1N1 called PA and NS. Two further genes from H1N1, NA and M, promoted airborne transmission to a lesser extent, and another, the NP gene, did so in combination with PA.
“It’s a very extensive paper,” says Schultz-Cherry. “It really shows that it’s more than just the HA. The other proteins are just as important and can drive transmission.” Chen says that health organisations should monitor wild viruses for the gene combinations that her team identified in the latest study. “If those kinds of reassortants are found, we’d need to pay high attention.”
[subsection: Knowledge gap]
It is unclear how the results apply to humans. Guinea pigs have bird-like receptor proteins in their upper airways in addition to mammalian ones, so reassortant viruses might bind in them more easily than they would in humans.
And scientists do not know whether the hybrid viruses are as deadly as the parent H5N1. The hybrids did not kill any of the guinea pigs they spread to, but Chen says that these rodents are not good models for pathogenicity in humans.
The yellow fever virus – a past standardized BW in the US Army, then carried by infected Aedes mosquitoes as vectors – was thus genetically engineered in conjunction with IAV, resulting in chimeric virions with infectious capacity for different biological systems (Oliveira et al., 2002).
Further, the anthrax protective antigen, which is one of the four proteins comprising the anthrax toxin, has been produced by an infective chimeric influenzaanthrax hybrid, thereby bringing about neutralizing antibody response against the toxin in mice (William et al., 2010). Similarly, a chimeric influenza virus expressing an epitope of outer membrane protein F of Pseudomonas aeruginosa was created and afforded protection against challenge with P. aeruginosa in a murine model (Staczek et al., 1998).
Besides yellow fever, a variety of pathogenic viruses have been engineered in conjunction with IAV. Functional chimeras were thus obtained between HIV type 1 Gp120 and IAV hemagglutinin; (Copeland, 2005) highly pathogenic avian influenza virus and murine leukemia virus; (Hatziioannou et al., 1998) hepatitis C virus E2 glycoprotein and IAV hemagglutinin; (Flint et al., 1999) and the gC glycoprotein of herpes simplex virus with another AIV HA (Lazarovits et al., 1996). All in all, the mastering of those remarkably developing techniques strongly illustrates the versatile applicability of IAV, and might lead to highly advanced military-oriented modifications.
"Certain laboratories in the institute have probably been engaged, in terms of research and development, in Chinese (biological weapons), at least collaterally, yet not as a principal facility of the Chinese BW alignment," Shoham told The Washington Times.
Work on biological weapons is conducted as part of a dual civilian-military research and is "definitely covert," he said.
In order to obtain a better understanding of the functional mechanisms involved in the fusogenesis of enveloped viruses, the influenza A (X31) and the yellow fever (17DD) virus particles were used to construct a chimeric structure based on their distinct pH requirements for fusion, and the distinct malleability of their nucleocapsids. The malleable nucleocapsid of the influenza A virus particle is characterized by a pleomorphic configuration when observed by electron microscopy. A heat inactivated preparation of X31 virus was used as a lectin to interact with the sialic acid domains present in the 17DD virus envelope. The E spikes of 17DD virus were induced to promote fusion of both envelopes, creating a double genome enveloped structure, the chimeric yellow fever-influenza A virus particle. These chimeric viral particles, originally denominated 'partículas virais quiméricas' (PVQ), were characterized by their infectious capacity for different biological systems. Cell inoculation with PVQ resulted in viral products that showed similar characteristics to those obtained after 17DD virus infections.
In late 1992, [...] Dr. Kanatjan Alibekov became the third defector from the Russian BW program. As the Deputy Director (number-two man) of Biopreparat and an infectious disease physician/epidemiologist, he was the highest ranking defector ever from the program. (Dr. Alibekov anglicized his name and now goes by Ken Alibek.) In 1999, Alibek published Biohazard, a first-hand detailed account of his experiences. Alibek disclosed a virtual encyclopedia of intimate details on Biopreparat from the top down [...]
In his book Biohazard, Alibek wrote about using plasmids to increase virulence or antibiotic resistance in bacteria. This corroborated Pasechnik‘s and ―Temple Fortune‘s‖ prior statements. He also discussed transfer of a gene for myelin toxin to Yersinia pestis (plague bacteria), however this agent was reportedly not yet weaponized. He said that a new Moscow-based company named Bioeffekt Ltd. had offered, by mail order, three strains of tularemia produced by ―technology unknown outside Russia‖ (i.e., genetically engineered strains). Most astounding of all, Alibek revealed that genetic engineering research was underway to create entirely new life forms. The goal of hybrid ―chimera viruses was to insert genes from one virus into another to create an even more lethal virus. Alibek stated that the Russians had created the first chimera virus from inserting DNA from Venezuelan equine encephalitis (VEE) virus into vaccinia virus (genetic structure almost identical to the smallpox virus). Chimeras, of VEE, Ebola, and Marburg genes inserted into the actual smallpox virus, were in the research phase when he left in 1991.
Making existing viruses more dangerous is on the second-highest tier, alongside making chemicals or biochemical by exploiting natural metabolic pathways. The lowest tier includes modifying the human genome using human gene drives.
