Rubella Virus Relatives Found in Diverse Animal Species

McDonnell Boehnen Hulbert & Berghoff LLP

McDonnell Boehnen Hulbert & Berghoff LLP

One of the hallmarks of the current coronavirus pandemic, caused by SARS-Cov-2, is its zoonotic origins.  The virus is thought to have risen in bats and "jumped" to humans, and despite conspiracy theories of intentional human engineering (reminiscent of Soviet-backed propaganda in Africa in the 1980's that HIV/AIDS was produced in a laboratory in the U.S. as a way to reduce the African population) such transfer of disease-causing microorganisms from animals to humans is not so rare.  Influenza, for example, is a virus that infects humans, fowl (chickens and ducks) and pigs, and due to the segmented nature of the influenza virus RNA genome passage through these species (with concomitant "shuffling" of genes for variants of the neuraminidase and hemagglutinin) results each year or so in a virus to which the human immune system is naïve, even for previously infected individuals.

Recently, an international* team of researchers reported in Nature their finding of viruses related to the Rubella virus (RuV) in a paper entitled "Relatives of rubella virus in diverse mammals," Nature 586: 424-28 (October 7, 2020).  One, named the ruhugu virus (RuhV), was found in "apparently healthy cyclops leaf-nosed bats (Hipposideros cyclops).  The other, a less closely related virus named the rustrela virus (RusV), is endemic in wild yellow-necked field mice (Apodemus flavicollis) in Germany.  This latter virus was also found by these researchers to cause acute encephalitis in placental and marsupial mammals (a donkey, Equus asinus; a capybara, Hydrochoeris hydrochaeris; and a kangaroo, Dendrolagus bennettianus) at a German zoo.

Genetic analyses showed clear homology of the genetic structure of these viruses, and the evolutionary relationships between them and the rubella virus that causes disease in humans.  The E1 protein of the RuV virus is described as "a receptor-binding, class-II fusion protein, contain[ing] an immune-reactive region (amino acid residue positions 202–283) with immunodominant T cell epitopes and four linear, neutralizing B cell epitopes (NT1–NT4)."  These researchers report that the E1 protein of the RusV and RuhV viruses share this structure and epitope mapping confirms the activity of neutralizing antibodies that block trimerization of this protein, which is necessary for virus fusion with host cell membrane.  Consistent with evolutionary divergence between RuV/RusV and RuhV are two non-conservative amino acid differences in one of the E1 protein fusion loops, disclosed as P134A and T135A.  Nevertheless, these researchers report "regions of marked conservation and stabilizing selection" in certain regions of the viral genomes, consistent with their putative evolutionary relationships.

While the authors are appropriately cautious in stating that "[t]he implication that RuhV or RusV are zoonotic agents is currently speculative," they also note that "bats and rodents possess biological attributes that predispose them to hosting many zoonotic viruses" and that RusV can infect both placental and marsupial mammals and cause neurological disease that resemble the severe encephalitis cause in infected human infants.

These observations are also relevant, the authors note, to efforts to eliminate rubella in infection (particularly congenital infections) in humans in the near future.  The possibility of future zoonotic transfer of these related viral species is a prospect that could influence the likelihood of realistically removing this class of viruses from human pathogens, and may in the interim provide a pathway for developing animal models for infection with these viruses.


* University of Wisconsin-Madison, WI; Uniformed Services University of the Health Sciences, Bethesda, MD; Leidos, Reston, VA; Fort Detrick, Frederick, MD; Friedrich-Loeffler-Institut, Greifswald-Insel Riems, DE; Food Safety and Fisheries, Rostock, DE

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