The current outbreak of Ebolavirus disease in Guinea, which began in February 2021, may have originated from a survivor of the 2013-16 outbreak in the same country.
Phylogenetic analysis of genome sequences revealed that viruses from the current outbreak group with the Makona variant, which caused the 2013-16 epidemic. The new isolates are most closely related to viruses sampled in the same region in August 2014, differing by only 12 and 13 bases. Consequently the recent outbreak in Guinea was not initiated by a spillover from an animal reservoir, as has been the case for all previously studied Ebolavirus outbreaks. Rather the sequence data indicate that the isolates are somehow linked to the 2013-16 outbreak. However, the number of substitutions – 110 – is far less than would be expected had the viruses been transmitted silently from human to human since that time.
The implication of these data is that Ebolavirus remained undetected in a survivor of the 2013-16 outbreak for 5 years. While Ebolavirus is an acute infection – one that is resolved in the host – the extent of the 2013-16 outbreak revealed rare instances of persistence of the virus in survivors. In once case, an individual who had recovered from the disease developed unilateral uveitis 14 weeks after the onset of Ebolavirus disease and 9 weeks after clearance of viremia. Infectious Ebolavirus was isolated from the aqueous humor. Shortly after the declaration of the end of the Ebolavirus outbreak in December 2015, a new cluster of cases was detected in Guinea in February and March 2016. Genome sequence analysis and epidemiological tracing revealed that these cases all originated from a single individual who harbored infectious Ebolavirus in his testes for over 500 days. He passed the infection on to others during sexual intercourse. In this outbreak the viral genomes differed by just 5 mutations from isolates obtained during the previous outbreak.
These observations indicate that Ebolavirus can persist, for at least 5 years, in an infectious form in immunoprivileged sites such as the vitreous humor of the eye and the testes. The slow evolutionary rate of the genome during such persistent infections – 6 times less than occurs during human to human transmission – implies a very low level of replication. It is remarkable that Ebolavirus retains infectivity for such long periods with so little reproduction.
Such persistent Ebolavirus infections are of concern as they may lead to new outbreaks after many years. The frequency of such persistence can reach 75% of men at 6 months after infection. Antiviral drugs should be developed to eliminate persistent infections in individuals who have recovered from Ebolavirus disease. Individuals harboring virus in semen are easy to identify, but detection of virus in the eye – done by sampling the vitreous humor by needle inserted into the eye – will be more difficult to accomplish.
Brian Hanley, PhD says
What I think is happening is that in vitreous humor, there is zero replication going on, or near zero. The vitreous humor is a near perfect virus preservation material. If virus is shed into it, the virus just sits there. Virus can slowly move in the vitreous humor by gravity. The direction of gravity changes in a cycle through the day depending on sleeping positions. With age, the humor becomes more liquid, which could enable the viruses to fall to the living cells of the eye more easily.
A similar mechanism must be happening in testes somewhere. The question is where exactly is it? I don’t think there is any other explanation. It could be determined in this individual by getting biopsies of tissues from scrotum, testes surrounding fluid, and various parts of the testes, perhaps walls of ducts, or prostate. This reminds me conceptually of when I was looking at an instrument with tubing, and figuring out where bacteria and microbeads were sticking – sometimes for years.
Benjamin M Blumberg, PhD says
Ebolavirus, like all viruses, can only replicate in cells that contain ribosomes and the other proteins involved in translation of mRNA. The aqueous humor is devoid of ribosomes (as far as I know) so Brian Hanley’s point about the virus eventually falling under the influence of gravity (1xg centrifugation) onto a cell is valid. In the context of re-ignition of an Ebola outbreak due to transmission of indolent virus in survivors’ semen, I would again like to mention that taking a scant tsp of CsCl mixed in a glass of juice (to dull the saltiness) once a day for 3-4 days, may be sufficient to stop such an Ebolavirus infection at its inception, and thus ward off the next epidemic. But CsCl seems to be too cheap or too common for anyone important to be concerned about, even though it is in limited clinical use.