ABSTRACT
Nucleic acid polymers (NAPs) are an attractive treatment modality for chronic hepatitis B (CHB), with REP2139 and REP2165 having shown efficacy in CHB patients. A subset of patients achieve functional cure, whereas the others exhibit a moderate response or are non-responders. NAP efficacy has been difficult to recapitulate in animal models, with the duck hepatitis B virus (DHBV) model showing some promise but remaining underexplored for NAP efficacy testing. Here we report on an optimized in vivo DHBV duck model and explore several characteristics of NAP treatment. REP2139 was efficacious in reducing DHBV DNA and DHBsAg levels in approximately half of the treated ducks, whether administered intraperitoneally or subcutaneously. Intrahepatic or serum NAP concentrations did not correlate with efficacy, nor did the appearance of anti-DHBsAg antibodies. Furthermore, NAP efficacy was only observed in experimentally infected ducks, not in endogenously infected ducks (vertical transmission). REP2139 add-on to entecavir treatment induced a deeper and more sustained virological response compared to entecavir monotherapy. Destabilized REP2165 showed a different activity profile with a more homogenous antiviral response followed by a faster rebound. In conclusion, subcutaneous administration of NAPs in the DHBV duck model provides a useful tool for in vivo evaluation of NAPs. It recapitulates many aspects of this class of compound's efficacy in CHB patients, most notably the clear division between responders and non-responders.
Subject(s)
Hepadnaviridae Infections , Hepatitis B Virus, Duck , Hepatitis B, Chronic , Hepatitis, Viral, Animal , Nucleic Acids , Animals , Humans , Hepatitis B Virus, Duck/genetics , Hepatitis B, Chronic/drug therapy , Antiviral Agents/pharmacology , Nucleic Acids/therapeutic use , Polymers/therapeutic use , Treatment Outcome , Ducks/genetics , DNA, Viral , Hepatitis, Viral, Animal/drug therapy , Hepatitis B virus , Hepadnaviridae Infections/drug therapy , Hepadnaviridae Infections/veterinary , LiverABSTRACT
African swine fever and swine erysipelas are two devastating diseases with similar manifestations ravaging the domestic pig industry. Only a single phylogenetic study has been carried out in Cameroon, and neither an extensive genotyping aimed at identifying the different serotypes nor has an appropriate differential diagnosis of different species of Erysipelothrix has been effected in ASF-infected animals. Of the 377 blood or tissue samples randomly collected from pig farms and slaughter slabs from January to August 2020, 120 were positive for ASFV (by PCR), giving a prevalence of 31.83%. Intragenomic resolution through sequencing divulged the presence of genotypes I, and Ia, two variants with 19 (ABNAAAACBNABTDBNAFA) and six (ABNAFA) tandem repeat sequences (TRS), serotype IV, and a single GGAATATATA repeat. The sole presence of E. tonsillarum (avirulent species) and not E. rhusiopathiae (virulent species) indicates that the severity observed during the 2020 ASF outbreak in the sampled regions was exclusively due to ASFV genotype I infection. Such characterisations are necessary for designing effective control measures and future potential vaccine candidates.
ABSTRACT
African swine fever (ASF) is a hemorrhagic contagious porcine disease caused by the African swine fever virus. The disease poses enormous problems to the pork industry with pig mortality ranging from 30% to 100%, depending on the virulence of the virus circulating. Cameroon, situated in Central Africa is one of the countries in which the African swine fever virus (ASFV) has been endemic since its first outbreak in 1982. The disease is a major problem to the pig industry causing huge economic losses. A clear and concise review on ASF in Cameroon relating to the entry and current genotype of the virus, epidemiology, pathogenesis and economic impact is lacking. A thorough literature search revealed: (1) The virus entered the country in 1982 and caused the death of 80% of the pigs. (2) All isolates belong to serogroup I and only Genotype I is circulating in Cameroon principally in the domestic cycle as there are neither soft ticks nor warthog in the pig production regions sampled. (3) 70% of the pig farmers are involved in the traditional system of production with local and hybrid breeds of pigs with minimal input. (4) The country is endemic to the virus with huge economic losses. (5) So far, very little research has been effected on ASFV in Cameroon. This review gives a detailed overview of the situation of African swine fever virus (ASFV) in the country along with potential avenues for future research into ASFV in Cameroon.
