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2021 Ebola Outbreak Resulted From Viral Latency, Reactivation, Genomic Study Finds

NEW YORK — A recent Ebola outbreak in Guinea may have been due to the resurgence of a persistent or latent infection from a prior epidemic that ended in 2016, according to a new sequencing analysis. This unexpected re-emergence could have ramifications for both public health and outbreak survivors.

Earlier this year, Guinea experienced an Ebola virus disease outbreak near Gouéké, which was also the epicenter of a previous epidemic that affected not only Guinea but also Sierra Leone and Liberia between December 2013 and June 2016. The latest outbreak began in mid-February 2021 and lasted through mid-June.

By sequencing samples collected from infected individuals during this latest Ebola outbreak, a team led by researchers in Guinea found that the new Zaire ebolavirus strains formed a phylogenetic cluster with samples from the 2013 to 2016 epidemic. As the recent viral lineage exhibited lower divergence from the previous epidemic than would be expected if the virus were circulating that whole time, the researchers concluded that the latest outbreak is likely due to a persistent infection with reduced replication or a period of latency, as they reported Wednesday in Nature.

"Prior to February 2021, it was assumed that contact between humans and wildlife was necessary for the Ebola virus to spread to the human population," first author Alpha Kabinet Keita from the University of Conakry and the University of Montpellier wrote in an email. "We learnt from the February 2021 Ebola outbreak that the virus could remain latent for a long time after infection in humans and reactivate itself to cause a relapse or a transmission that would lead to a new outbreak."

He and his colleagues collected blood samples from 14 patients with confirmed Ebola Zaire from the new outbreak for sequencing. Three laboratories using different approaches sequenced each sample, and data from the three labs was pooled to construct 12 high-quality Ebola virus genomes that covered between 82.9 percent and 99.9 percent of the reference genome.

A maximum likelihood phylogenetic reconstruction analysis placed the genomes from the 2021 Ebola outbreak in Guinea as a single cluster within the Ebola viruses from the 2013 to 2016 epidemic. These newer genomes also shared 10 substitutions that arose during the previous epidemic, providing additional evidence that the two outbreaks are connected and that the new cases are not due to an animal spillover event.

However, there was a low number of other substitutions distinguishing the 2021 cluster branch from the earlier viruses. These 12 changes are fewer than what would be expected if the virus had undergone human-to-human transmission in the intervening years, the researchers noted. Instead, they suggested that the virus re-emerged following some form of latency or dormancy during persistent infection.

This finding indicates that people could serve as reservoirs of the Ebola virus, Tulane University School of Medicine's Robert Garry wrote in an accompanying commentary in Nature, adding that it is not surprising that the virus re-emerged in Guinea, which has a large number of Ebola survivors. He noted that viral persistence has been uncovered in some Ebola survivors but that it is unclear how the virus can be reactivated.

Keita and his colleagues wrote in their paper that their findings stress the importance of caring for and supporting Ebola survivors, though in a way that is not stigmatizing. "In addition to consciousness-raising, a multidisciplinary protocol must be developed that integrates clinical, biological, and psycho-social monitoring, with a central place for anthropologists and effective involvement of the population in the monitoring process," Keita said.

He added that his team is working on understanding the immunological determinants of viral reactivation.

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