番茄社区

BOSTON -- Italian researchers are trying to unravel a frightening mystery: How did a European laboratory worker become infected with human immunodeficiency virus (HIV) from a non-infectious strain?

"We are looking at a perfect storm of errors,", a researcher at the University of Rome Tor Vergata, told 番茄社区. "We cannot exclude any mode of infection at this time."

At the annual Conference on Retroviruses and Opportunistic Infections, she explained that her laboratory was asked to investigate the incident, which did not occur in Italy.

The infected laboratory worker -- whose identity, including sex and age, are being withheld -- only found out about the infection when the person was tested in the process of donating blood and was determined to have active HIV infection. The worker denied all the known risk factors: no sexual behavior consistent with HIV infection, monogamous sex partner was HIV-negative, no injection or IV drug use, and no history of blood transfusions or invasive medical procedures.

Adding to the mystery, the laboratory worker also said that no laboratory accidents had occurred. The worker did not recall any broken gloves, cell medium splash, percutaneous injury such as a needle stick, or anything else that might have caused an exposure.

Yet, Alteri and her colleagues found, the genetic sequence of the HIV virus in the worker's body was almost identical to an HIV construct that the worker was using in experiments in the Biosafety Level 2 laboratory. That construct was not supposed to be infectious.

The investigators believe that somehow a competent HIV virus from a Biosafety-3 laboratory found its way into the lower-safety level laboratory. That in itself might not have caused the infection, but also present were experiments using the vesicular stomatitis virus (VSV) -- a highly infectious pathogen that is related to the rabies virus and is often used in laboratory experiments as an infection vector.

The laboratory worker was conducting pseudotyping procedures that required plasmid encoding for the G glycoprotein of VSV, Alteri said. VSV can increase virus infectivity 20- to 130-fold, she said.

What happened next is speculation, the researchers said. They think that, somehow, the competent HIV virus was able to share its genes with the non-infective construct, rendering the construct infectious. And that, in turn, became attached to the VSV.

"VSV can infect any cell in the body," said molecular biologist , of Tufts University in Boston. "So it is possible that the virus infected the worker through direct contact or through the lungs if the virus was in an aerosol form," he told 番茄社区.

What the researchers do know, Alteri reported in her oral presentation and at a press conference, is:

• "HIV-1 contagion occurred in the period when the person was working on HIV-1 pseudoviruses production with defective constructs in a bio-safety 2 laboratory containment."
• "All those procedures should not have included any infective vector."
• "Nevertheless, an infectious HIV-1, NL4.3/JRFL molecular clone, probably present in the laboratory at the time, entered the chain of HIV-1 pseudoviruses that the worker was handling, most likely causing the infection."

What Alteri and her colleagues have not confirmed is when and how the infectious molecular clone entered the pseudoviruses production; what was the mode of contagion since no reported event that might explain what happened has ever been reported or recalled; and if the use of the VSV favored the contagion.

The bottom line, though, is the worker is now HIV-positive and is being treated with antiretroviral therapy, and will have to continue that treatment for life, assuming a definitive cure for the disease is not discovered.

"This is an interesting and disturbing case," Coffin said as he moderated the press conference, "of an individual in an research laboratory who through a series of rather inadvertent accidents became infected with HIV."

He said the episode suggests that, in some laboratories, "there has been a little bit too much familiarity with the use of HIV vectors, which can be very valuable in gene therapy. I think there has been a certain amount of biosafety fatigue in laboratories that needs to be revisited by institutional biosafety committees. These kinds of accidents just shouldn't happen."

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