Rat hepatitis E virus (Rocahepevirus ratti) in people living with HIV

Abstract

Rat hepatitis E virus (ratHEV; species Rocahepevirus ratti) is considered a newly emerging cause of acute hepatitis of zoonotic origin. ratHEV infection of people living with HIV (PLWH) might portend a worse, as with hepatitis E virus (HEV; species Paslahepevirus balayani), and consequently this group may constitute a high-risk population. We aimed to evaluate the prevalence of ratHEV by measuring viral RNA and specific IgG antibodies in a large Spanish cohort of PLWH. Multicentre study conducted in Spain evaluating PLWHIV included in the Spanish AIDS Research Network (CoRIS). Patients were evaluated for ratHEV infection using PCR at baseline and anti-ratHEV IgG by dot blot analysis to evaluate exposure to ratHEV strains. Patients with detectable ratHEV RNA were followed-up to evaluate persistence of viremia and IgG seroconversion. Eight-hundred and forty-two individuals were tested. A total of 9 individuals showed specific IgG antibodies against ratHEV, supposing a prevalence of 1.1 (95% CI; 0.5%-2.1%). Of these, only one was reactive to HEV IgG antibodies by ELISA. One sample was positive for ratHEV RNA (prevalence of infection: 0.1%; 95% CI: 0.08%-0.7%). The case was a man who had sex with men exhibiting a slightly increased alanine transaminase level (49 IU/L) as only biochemical alteration. In the follow-up, the patients showed undetectable ratHEV RNA and seroconversion to specific ratHEV IgG antibodies. Our study shows that ratHEV is geographical broadly distributed in Spain, representing a potential zoonotic threat.

Keywords: HIV; Hepatitis E; Zoonoses; acute hepatitis; public health; rat hepatitis E virus.

Figure 1.

Validation of the dot blot for the detection of HEV genotype 3 and ratHEV IgG specific antibodies. Carboxy-terminal segments of the capsid proteins were used as antigen for HEV genotype 3 and ratHEV in the first and second spot (HEV and ratHEV), respectively. As negative control (C-) a nucleocapsid protein derivative of Puumala orthohantavirus strain Vranica/Hällnäs was used. As positive control, we used an E. coli M15 lysate (C+).

Figure 2.

Geographical distribution of patients tested for ratHEV RNA and IgG specific antibodies.

Figure 3.

Phylogenetic analysis of the sequence identified in the study. Sequence of the patient identified in the present study is marked with a circle (•), human cases and rodents’ strains identified previously in Spain with a triangle (▴). In bold its highlighted strains identified in humans. The evolutionary history was inferred by using the Maximum Likelihood method based on the Tamura-Nei model. The bootstrap consensus tree inferred from 1,500 replicates is taken to represent the evolutionary history of the taxa analyzed. Branches corresponding to partitions reproduced in less than 50% bootstrap replicates are collapsed. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using the Maximum Composite Likelihood (MCL) approach, and then selecting the topology with superior log likelihood value. The analysis involved 102 nucleotide sequences. Codon positions included were 1st + 2nd + 3rd + Noncoding. All positions containing gaps and missing data were eliminated. There are a total of 221 positions in the final dataset.

Figure 4.

DB results for the 9 positive ratHEV IgG antibodies sera. The numbers correspond to the ID of the sample.