Limited Intrahost Diversity and Background Evolution Accompany 40 Years of Canine Parvovirus Host Adaptation and Spread.

Canine parvovirus (CPV) is a highly successful pathogen that has sustained pandemic circulation in dogs for more than 40 years. Here, integrating full-genome and deep-sequencing analyses, structural information, and in vitro experimentation, we describe the macro- and microscale features that accompany CPV's evolutionary success. Despite 40 years of viral evolution, all CPV variants are more than ∼99% identical in nucleotide sequence, with only a limited number (<40) of substitutions becoming fixed or widespread during this time. Notably, most substitutions in the major capsid protein (VP2) gene are nonsynonymous, altering amino acid residues that fall within, or adjacent to, the overlapping receptor footprint or antigenic regions, suggesting that natural selection has channeled much of CPV evolution. Among the limited number of variable sites, CPV genomes exhibit complex patterns of variation that include parallel evolution, reversion, and recombination, compromising phylogenetic inference. At the intrahost level, deep sequencing of viral DNA in original clinical samples from dogs and other host species sampled between 1978 and 2018 revealed few subconsensus single nucleotide variants (SNVs) above ∼0.5%, and experimental passages demonstrate that substantial preexisting genetic variation is not necessarily required for rapid host receptor-driven adaptation. Together, these findings suggest that although CPV is capable of rapid host adaptation, a relatively low mutation rate, pleiotropy, and/or a lack of selective challenges since its initial emergence have inhibited the long-term accumulation of genetic diversity. Hence, continuously high levels of inter- and intrahost diversity are not necessarily required for virus host adaptation.IMPORTANCE Rapid mutation rates and correspondingly high levels of intra- and interhost diversity are often cited as key features of viruses with the capacity for emergence and sustained transmission in a new host species. However, most of this information comes from studies of RNA viruses, with relatively little known about evolutionary processes in viruses with single-stranded DNA (ssDNA) genomes. Here, we provide a unique model of virus evolution, integrating both long-term global-scale and short-term intrahost evolutionary processes of an ssDNA virus that emerged to cause a pandemic in a new host animal. Our analysis reveals that successful host jumping and sustained transmission does not necessarily depend on a high level of intrahost diversity nor result in the continued accumulation of high levels of long-term evolution change. These findings indicate that all aspects of the biology and ecology of a virus are relevant when considering their adaptability.

Protective effects of kolaviron and gallic acid against cobalt-chloride-induced cardiorenal dysfunction via suppression of oxidative stress and activation of the ERK signaling pathway.

Cobalt (Co) toxicity is a potential public health problem due to recent renewed use of Co in orthopedic implants, dietary supplements, and blood doping in athletes and horses. We investigated the protective roles of kolaviron (KV), a bi-flavonoid of Garcinia kola, and gallic acid (GA) on cobalt chloride (CoCl2)-induced cardiorenal damage in rats. CoCl2 caused significant increases (p < 0.05) in serum creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate transaminase (AST), xanthine oxidase (XO), urea, creatinine, malondialdehyde, H2O2, nitric oxide, as well as C-reactive protein expression, along with significant (p < 0.05) reduction in cardiac and renal expression of extracellular signal regulated kinase (ERK) and the activities of superoxide dismutase, catalase, and glutathione S-transferase. KV and GA prevented the toxic effects of CoCl2 by stimulating ERK expression and reversing Co-induced biochemical changes. Administration of CoCl2 alone did not significantly alter ECG patterns in the rats, although co-treatment with KV (200 mg/kg) produced QT-segment prolongation and also appeared to potentiate Co hypotension. Histopathology of the heart and kidneys of rats treated with KV and GA confirmed the biochemical data. KV and GA thus protected against cardiac and renal damage in Co intoxication via antioxidant and (or) cell survival mechanisms, possibly involving ERK activation.

Cyclophosphamide-induced Hepatotoxicity in Wistar Rats: The Modulatory Role of Gallic Acid as a Hepatoprotective and Chemopreventive Phytochemical.

BACKGROUND: Gallic acid (GA) is an endogenous plant phenol known to have antioxidant, free radical scavenging ability, anti-inflammatory, anti-cancer, and anti-fungal properties. The aim of this study was to assess the protective effect of GA on cyclophosphamide (CPA)-induced hepatotoxicity in male Wistar rats. METHODS: Sixty rats were grouped into six groups of 10 rats per group. Group 1 received distilled water. Group 2 received CPA at 200 mg/kg single dose intraperitoneally on day 1. Groups 3 and 4 received a single dose of CPA (200 mg/kg) intraperitoneally on day 1 and then were treated with GA at 60 and 120 mg/kg body weight for 14 days, respectively. Rats in Groups 5 and 6 only received GA at 60 and 120 mg/kg body weight for 14 days, respectively. GA was administered orally. RESULTS: CPA induced hepatic damage as indicated by significant elevation (P < 0.05) in aspartate aminotransferase, organ weight, and evidence by the histological study. CPA also induced hepatic oxidative stress as indicated by significant elevation (P < 0.05) in malondialdehyde content, hydrogen peroxide (H2O2) generation, nitrite level, and the level of glutathione (GSH) peroxidase crashed in the CPA-treated group. GA enhanced the antioxidant defense system as indicated by significant elevation (P < 0.05) in GSH level, catalase activity, and GSH-S-transferase activity. CONCLUSIONS: Taken together, the result of this present study shows that GA has a protective effect on CPA-induced hepatotoxicity.

Mycobacterium tuberculosis and Dual M. tuberculosis/M. bovis Infection as the Cause of Tuberculosis in a Gorilla and a Lioness, Respectively, in Ibadan Zoo, Nigeria.

Tuberculosis (TB) in zoo animals is an important public health problem in places where it occurs. This is even very important in countries where there is little public health awareness about the disease; thus confined animals in the zoo can be infected directly or indirectly by infected humans and vice versa. In Nigeria, the problem of TB is a major concern among both humans and cattle. Here, we present cases of Mycobacterium tuberculosis and M. tuberculosis/M. bovis infections in a female gorilla and a lioness, respectively, in a zoo in Ibadan, Nigeria. These cases were confirmed after bacteriological examinations and DNA from granulomatous lesions of the animals' carcasses were subjected to the Hain and spoligotyping techniques. Our findings reveal the first documented report of TB infections in a gorilla and a lioness in zoo animals in Nigeria. The public health risks of tuberculosis in zoological settings are therefore reemphasized.

Gastrointestinal protective efficacy of Kolaviron (a bi-flavonoid from Garcinia kola) following a single administration of sodium arsenite in rats: Biochemical and histopathological studies.

BACKGROUND: Arsenic intoxication is known to produce symptoms including diarrhea and vomiting, which are indications of gastrointestinal dysfunction. OBJECTIVE: We investigated whether Kolaviron (KV) administration protected against sodium arsenite (NaAsO2)-induced damage to gastric and intestinal epithelium in rats. MATERIALS AND METHODS: Control rats (Group I) were given a daily oral dose of corn oil. Rats in other groups were given a single dose of NaAsO2 (100 mg/kg; intraperitoneal) alone (Group II) or after pretreatment for 7 days with KV at 100 mg/kg (Group III) and 200 mg/kg (Group IV). Rats were sacrificed afterward and portions of the stomach, small intestine and colon were processed for histopathological examination. Hydrogen peroxide, reduced glutathione, malondialdehyde (MDA) concentrations as well as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione S-transferase (GST) and myeloperoxidase (MPO) were measured in the remaining portions of the different gastrointestinal tract (GIT) segments. RESULTS: NaAsO2 caused significant increases (P < 0.05) in MDA levels and MPO activity, with significant reductions (P < 0.05) in GST, GPX, CAT and SOD activities in the stomach and intestines. KV significantly reversed the changes (P < 0.05) in a largely dose-dependent manner. The different segments had marked inflammatory cellular infiltration, with hyperplasia of the crypts, which occurred to much lesser degrees with KV administration. CONCLUSION: The present findings showed that KV might be a potent product for mitigating NaAsO2 toxicity in the GIT.

Factors associated with probable cluster of leptospirosis among kennel workers in Abuja, Nigeria.

INTRODUCTION: Between February and October 2009 an increase in morbidity and mortality in dogs in a national kennel in Abuja, Nigeria, was observed with signs indicative of leptospirosis. Concurrent illness was observed in some kennel workers which had high titres of leptospira antibodies. METHODS: An unmatched case-control study was conducted to identify associated factors. Fifteen cases and fifteen controls were recruited. A probable case was defined as any person working at the kennel with history of fever, chills, headache, myalgia with either conjunctivitis or sore throat between February and December 2009. Controls were healthy kennel workers within the same period. Inclusion criteria were any person meeting the definition (for both cases and controls). Kennel workers who were sick but did not fit into the case definition were excluded. RESULTS: Bivariate analysis showed that wounds or cuts on either hands or legs of kennel workers during the period of the outbreak and contact with sewage at the kennel together (p = 0.001) was associated with leptospirosis among kennel workers. CONCLUSION: The findings revealed the importance of environmental hygiene in the prevention and control of leptospirosis. Sanitation and hygiene improvements were recommended.

A PCR-based epidemiological survey of Hepatozoon canis in dogs in Nigeria.

The prevalence of Hepatozoon canis infections in dogs in Nigeria was surveyed using molecular methods. DNA was extracted from blood samples obtained from 400 dogs. A primer set that amplified the Babesia canis 18S rRNA gene, which has high similarity to the H. canis 18S rRNA gene, was used for the PCR. As a result, samples from 81 dogs (20.3%) produced 757 bp bands, which differed from the 698 bp band that corresponded to B. canis infection. The sequence of the PCR products of 10 samples were determined, all of which corresponded with the H. canis sequence.

Molecular survey of Babesia canis in dogs in Nigeria.

An epidemiological study of Babesia canis in dogs in Nigeria was performed. Four hundred blood samples collected from dogs in Nigeria were investigated using nested PCR and sequence analysis. On nested PCR screening, nine samples (2.3%) produced a band corresponding to a 698-bp fragment indicative of B. canis infection. Sequence analysis of the PCR products identified eight samples (2.0%) as B. canis rossi and the ninth (0.3%) as B. canis vogeli. This is the first report of the prevalence of B. canis rossi and B. canis vogeli in dogs in Nigeria.