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Lab worker contracts HIV through unknown transmission route
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A laboratory worker performing routine experiments involving HIV-1 pseudoviruses was infected with a replication-competent recombinant clone that was inadvertently introduced in a biosafety level-2 containment, according to recent findings published in Clinical Infectious Diseases.
Although researchers identified the source of infection, the mode of transmission remains unknown.
“Here we describe for the first time an HIV-1 infection of a laboratory worker with a replication-competent recombinant clone,” Alessandro Soria, MD, of the division of infectious diseases at San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy, and colleagues wrote. “The relevant novelty, which differentiates this case from other rare laboratory accidents (where laboratory workers consciously had handled infectious viral cultures) is that the patient described here was supposed to exclusively manage constructs that were per se noninfectious, with restrictions for [biosafety level-2 (BSL-2)], and that an unaware contamination by recombinant clone caused the infection.”
The lab worker’s infection was first identified during routine HIV screening. Six months prior to the diagnosis, the worker was assigned a task to produce nonreplication-competent viruses, or pseudoviruses, that are used in laboratories to construct viral particles for gene-delivery, drug-screening and HIV replication studies.
The experiments were conducted in BSL-2 conditions. The worker did not recall any accidents, including percutaneous injuries, splashes, breaking of gloves and eye or skin exposure to contents. Access to BSL-3 conditions was prohibited and not reported.
Full-length HIV-DNA sequencing was performed to identify the source of infection. A phylogenetic analysis revealed that the lab worker’s virus was similar to the HIV-1 constructs the worker had handled. The researchers concluded that the infection was likely caused by contamination or a labeling error of an infective clone that was being used by other researchers in the BSL-3 containment of the laboratory at the same time. A slow progression of viral load and genetic evolution demonstrated that a pure laboratory recombinant clone had adapted to a human host.
“This case is disturbing for the unexplained route of virus transmission,” Soria and colleagues wrote. “Notwithstanding these limitations, this case warns of potential hazard in research laboratories where multiple HIV-derived constructs are managed.” – by Stephanie Viguers
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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The preparation that this lab worker was using was thought to be highly defective and missing genes that are necessary for replication. The lab worker used another gene from a vesicular stomatitis virus (VSV) that allows viral particles to enter cells, giving lentiviral vectors the property to be much more stable and infectious than if they were carrying the normal HIV envelope gene. What seems to have happened in this case is that the lab worker inadvertently got a hold of a different construct that, in fact, had a complete and infectious HIV genome and was able to produce replication-competent virus.
The lab worker performed a transfection as though they were handling a defective virus. There was, as far as anybody can tell, absolutely no break in technique. The idea, although it remains to be proven and needs to be followed up, is that the presence of this VSV-G protein may have made the virus much more infectious via some route that HIV is not ordinarily transmitted. There are no cases of such transmission that have been reported, as far as I know, but it is possible that by having this additional envelope protein, the virus was much more accessible for infection — either by aerosol or droplets on the skin — by means where pure HIV would not be transmissible. This is something that needs to be looked at very carefully by institute biosafety committees and by regulatory authorities to perhaps revise the guidelines recommended for working with some of these viruses that had been previously considered to be quite safe.
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