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acute infection

Five year persistence of Ebolavirus in humans

18 March 2021 by Vincent Racaniello

Ebolavirus

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.

Filed Under: Basic virology Tagged With: acute infection, ebolavirus, Guinea, persistent infection, sexual transmission, viral, virology, virus, viruses

Virology lecture #17: Acute infections

20 April 2010 by Vincent Racaniello


Download: .wmv (322 MB) | .mp4 (91 MB)

Visit the virology W3310 home page for a complete list of course resources.

Filed Under: Basic virology, Information Tagged With: acute infection, influenza, lecture, polio, rotavirus, viral, virology, virus, w3310, West Nile virus

Antigenic variation explains recurring acute infections

18 February 2009 by Vincent Racaniello

antigenic-mapThe rapid clearance of acute viral infections is a consequence of robust host defenses. Survivors of acute infections are usually immune to infection with the same virus. If the immune response is so effective, why do some viral infections – such as the common cold or influenza – occur repeatedly?

Acute infections recur because selection pressure in the host leads to the production of virions that are resistant to clearance by the immune system. For example, when viruses replicate in the presence of antibodies that can block infectivity (neutralizing antibodies), viruses are selected that are resistant to the antibodies. These viruses can then infect individuals who are immune to the original virus. The ability to escape antibody neutralization requires structural plasticity – the ability to tolerate many amino acid changes in virion structural proteins without losing infectivity. Examples of viruses with this attribute are influenza virus and HIV.

While some viruses have remarkable structural plasticity, others tolerate few amino acid changes. We have little understanding of the principles that govern these differences. The limited structural variation of poliovirus (3 serotypes) is in stark contrast to the virions of rhinovirus, which have remarkable structural plasticity (~100 serotypes); yet the two viruses are both members of the Picornaviridae.  Whether or not the virion is enveloped is of no consequence: influenza, measles, and yellow fever virions are all enveloped, yet antibody-resistant variants of the latter two viruses are rarely observed.

The practical consequences of structural plasticity are quite clear: they determine whether or not immunization confers sustained protection against infection. The poliovirus, yellow fever, and measles virus vaccines, which have not been changed significantly since they were first developed, induce immunity that lasts a lifetime. In contrast, a new influenza vaccine is needed every year, and no one has yet determined how to formulate a vaccine that protects against all 100 rhinovirus serotypes.

The change of virion proteins in response to antibody selection is called antigenic variation. There are two kinds: antigenic drift, comprising minor amino acid changes such as those which necessitate a new influenza vaccine each year, and antigenic shift. The latter involves acquisition of new structural proteins and a major change in antigenic properties such that the virus is no longer recognized by antibodies in the population. Such ‘shifted’ strains of influenza virus arise periodically when genes encoding structural proteins are acquired from viruses that infect animal hosts. These strains cause worldwide epidemics of influenza that are called pandemics.

Antigenic evolution has been visualized by creating two-dimensional maps in a process called antigenic cartography. These maps are made with data that provide information on the antigenic properties of the pathogen. In the case of influenza virus, the data come from measuring the ability of an antiviral antibody to inhibit hemagglutination – binding of virions to red blood cells. Such maps show how amino acid changes can affect antibody binding to virus particles, which cannot be done by comparing nucleotide sequences of different virus isolates. By charting influenza virus strains in this way, it should be possible to better understand genetic and antigenic evolution.

J. C. de Jong, D. J. Smith, A. S. Lapedes, I. Donatelli, L. Campitelli, G. Barigazzi, K. Van Reeth, T. C. Jones, G. F. Rimmelzwaan, A. D. M. E. Osterhaus, R. A. M. Fouchier (2007). Antigenic and Genetic Evolution of Swine Influenza A (H3N2) Viruses in Europe Journal of Virology, 81 (8), 4315-4322 DOI: 10.1128/JVI.02458-06

D. J. Smith (2004). Mapping the Antigenic and Genetic Evolution of Influenza Virus Science, 305 (5682), 371-376 DOI: 10.1126/science.1097211

Filed Under: Information Tagged With: acute infection, antigenic cartography, antigenic variation, evolution, influenza

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