Rocahepevirus ratti as an Emerging Cause of Acute Hepatitis Worldwide

Abstract

The hepatitis E virus (HEV) is a widespread human infection that causes mainly acute infection and can evolve to a chronic manifestation in immunocompromised individuals. In addition to the common strains of hepatitis E virus (HEV-A), known as Paslahepevirus balayani, pathogenic to humans, a genetically highly divergent rat origin hepevirus (RHEV) can cause hepatitis possessing a potential risk of cross-species infection and zoonotic transmission. Rocahepevirus ratti, formerly known as Orthohepevirus C, is a single-stranded RNA virus, recently reassigned to Rocahepevirus genus in the Hepeviridae family, including genotypes C1 and C2. RHEV primarily infects rats but has been identified as a rodent zoonotic virus capable of infecting humans through the consumption of contaminated food or water, causing both acute and chronic hepatitis cases in both animals and humans. This review compiles data concluding that 60% (295/489) of RHEV infections are found in Asia, being the continent with the highest zoonotic and transmission potential. Asia not only has the most animal cases but also 16 out of 21 human infections worldwide. Europe follows with 26% (128/489) of RHEV infections in animals, resulting in four human cases out of twenty-one globally. Phylogenetic analysis and genomic sequencing will be employed to gather global data, determine epidemiology, and assess geographical distribution. This information will enhance diagnostic accuracy, pathogenesis understanding, and help prevent cross-species transmission, particularly to humans.

Keywords: HEV-C; Orthohepevirus C; RHEV; Rocahepevirus ratti; hepatitis E; rodent; zoonosis.

Figure 1

Phylogenetic tree of members of the family Hepeviridae, subfamily Orthohepevirinae (ORF1 polyprotein residues 1–450) (https://ictv.global/report/chapter/hepeviridae/hepeviridae, accessed on 31 October 2023).

Figure 2

Selection of studies about Rocahepevirus ratti, including its epidemiology, 2000–2023. This selection was made for inclusion of studies in the bibliographic review. It was necessary to consider the fact that Orthohepevirus C has been renowned as Rocahepevirus ratti in recent studies (2022 and 2023).

Figure 3

Hepatitis E virus (HEV-A) genome structure, including its open reading frames (ORFs) and proteins. Contains a single-stranded positive-sense RNA molecule approximately 7.2 kb long and is presented in the genome of the virus of HEV-A. It displays a 7-methylguanosine RNA at the 5′ end and poly-A at the 3′ terminus. All HEV strains contain three open reading frames (ORFs): ORF1, ORF2, and ORF3 (an additional ORF4(?) region is found which functionality is not totally understood). ORF1 produces non-structural polyproteins for viral replication and transcription such as (Met), Y-domain, (PCP), (HVR), (Hel), and (RdRp). ORF2 encodes the capsid protein, while ORF3 encodes a multifunctional phosphoprotein, known as VP13. These proteins from ORF2 and ORF3 exhibit partial overlap and are translated from a subgenomic RNA with 2.2 kb in length. Additionally, ORF4 gives rise to an internal ribosome entry site-like protein (IRES) to respond to the stress generated in the endoplasmic reticulum (ER). ORF4 is an enhancer of viral replication. (GenBank accession number AF444002.1) [10,13,14].

Figure 4

Map of animal infections caused by Rocahepevirus ratti in different countries. The darker the color, the greater the number of infections.