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Rift Valley fever phlebovirus (RVFV) infects humans and a wide range of ungulates and historically has caused devastating epidemics in Africa and the Arabian Peninsula. Lesions of naturally infected cases of Rift Valley fever (RVF) have only been described in detail in sheep with a few reports concerning cattle and humans. The most frequently observed lesion in both ruminants and humans is randomly distributed necrosis, particularly in the liver. Lesions supportive of vascular endothelial injury are also present and include mild hydropericardium, hydrothorax and ascites; marked pulmonary congestion and oedema; lymph node congestion and oedema; and haemorrhages in many tissues. Although a complete understanding of RVF pathogenesis is still lacking, antigen-presenting cells in the skin are likely the early targets of the virus. Following suppression of type I IFN production and necrosis of dermal cells, RVFV spreads systemically, resulting in infection and necrosis of other cells in a variety of organs. Failure of both the innate and adaptive immune responses to control infection is exacerbated by apoptosis of lymphocytes. An excessive pro-inflammatory cytokine and chemokine response leads to microcirculatory dysfunction. Additionally, impairment of the coagulation system results in widespread haemorrhages. Fatal outcomes result from multiorgan failure, oedema in many organs (including the lungs and brain), hypotension, and circulatory shock. Here, we summarize current understanding of RVF cellular tropism as informed by lesions caused by natural infections. We specifically examine how extant knowledge informs current understanding regarding pathogenesis of the haemorrhagic fever form of RVF, identifying opportunities for future research.
Lieza Odendaal; A Davis; Estelle Venter. Insights into the Pathogenesis of Viral Haemorrhagic Fever Based on Virus Tropism and Tissue Lesions of Natural Rift Valley Fever. Viruses 2021, 13, 709 .
AMA StyleLieza Odendaal, A Davis, Estelle Venter. Insights into the Pathogenesis of Viral Haemorrhagic Fever Based on Virus Tropism and Tissue Lesions of Natural Rift Valley Fever. Viruses. 2021; 13 (4):709.
Chicago/Turabian StyleLieza Odendaal; A Davis; Estelle Venter. 2021. "Insights into the Pathogenesis of Viral Haemorrhagic Fever Based on Virus Tropism and Tissue Lesions of Natural Rift Valley Fever." Viruses 13, no. 4: 709.
Infection with Rift Valley fever phlebovirus (RVFV) causes abortion storms and a wide variety of outcomes for both ewes and fetuses. Sheep fetuses and placenta specimens were examined during the 2010–2011 River Valley fever (RVF) outbreak in South Africa. A total of 72 fetuses were studied of which 58 were confirmed positive for RVF. Placenta specimens were available for 35 cases. Macroscopic lesions in fetuses were nonspecific and included marked edema and occasional hemorrhages in visceral organs. Microscopically, multifocal hepatic necrosis was present in 48 of 58 cases, and apoptotic bodies, foci of liquefactive hepatic necrosis (primary foci), and eosinophilic intranuclear inclusions in hepatocytes were useful diagnostic features. Lymphocytolysis was present in all lymphoid organs examined with the exception of thymus and Peyer’s patches, and pyknosis or karyorrhexis was often present in renal glomeruli. The most significant histologic lesion in the placenta was necrosis of trophoblasts and endothelial cells in the cotyledonary and intercotyledonary chorioallantois. Immunolabeling for RVFV was most consistent in trophoblasts of the cotyledon or caruncle. Other antigen-positive cells included hepatocytes, renal tubular epithelial, juxtaglomerular and extraglomerular mesangial cells, vascular smooth muscle, endothelial and adrenocortical cells, cardiomyocytes, Purkinje fibers, and macrophages. Fetal organ samples for diagnosis must minimally include liver, kidney, and spleen. From the placenta, the minimum recommended specimens for histopathology include the cotyledonary units and caruncles from the endometrium, if available. The diagnostic investigation of abortion in endemic areas should always include routine testing for RVFV, and a diagnosis during interepidemic periods might be missed if only limited specimens are available for examination.
Lieza Odendaal; Sarah J. Clift; Geoffrey T. Fosgate; A. Sally Davis. Ovine Fetal and Placental Lesions and Cellular Tropism in Natural Rift Valley Fever Virus Infections. Veterinary Pathology 2020, 57, 791 -806.
AMA StyleLieza Odendaal, Sarah J. Clift, Geoffrey T. Fosgate, A. Sally Davis. Ovine Fetal and Placental Lesions and Cellular Tropism in Natural Rift Valley Fever Virus Infections. Veterinary Pathology. 2020; 57 (6):791-806.
Chicago/Turabian StyleLieza Odendaal; Sarah J. Clift; Geoffrey T. Fosgate; A. Sally Davis. 2020. "Ovine Fetal and Placental Lesions and Cellular Tropism in Natural Rift Valley Fever Virus Infections." Veterinary Pathology 57, no. 6: 791-806.
A clear distinction can be made regarding the susceptibility to and the severity of lesions in young lambs when compared to adult sheep. In particular, there are important differences in the lesions and tropism of Rift Valley fever virus (RVFV) in the liver, kidneys, and lymphoid tissues of young lambs. A total of 84 lambs (
Lieza Odendaal; A. Sally Davis; Geoffrey Fosgate; Sarah J. Clift. Lesions and Cellular Tropism of Natural Rift Valley Fever Virus Infection in Young Lambs. Veterinary Pathology 2019, 57, 66 -81.
AMA StyleLieza Odendaal, A. Sally Davis, Geoffrey Fosgate, Sarah J. Clift. Lesions and Cellular Tropism of Natural Rift Valley Fever Virus Infection in Young Lambs. Veterinary Pathology. 2019; 57 (1):66-81.
Chicago/Turabian StyleLieza Odendaal; A. Sally Davis; Geoffrey Fosgate; Sarah J. Clift. 2019. "Lesions and Cellular Tropism of Natural Rift Valley Fever Virus Infection in Young Lambs." Veterinary Pathology 57, no. 1: 66-81.
Sporadic outbreaks of Rift Valley fever virus (RVFV), a zoonotic, mosquito-borne Phlebovirus, cause abortion storms and death in sheep and cattle resulting in catastrophic economic impacts in endemic regions of Africa. More recently, with changes in competent vector distribution, growing international trade, and its potential use for bioterrorism, RVFV has become a transboundary animal disease of significant concern. New and sensitive techniques that determine RVFV presence, while lessening the potential for environmental contamination and human risk, through the use of inactivated, noninfectious samples such as formalin-fixed, paraffin-embedded (FFPE) tissues are needed. FFPE tissue in situ hybridization (ISH) enables the detection of nucleic acid sequences within the visual context of cellular and tissue morphology. Here, we present a chromogenic pan-RVFV ISH assay based on RNAscope® technology, which is able to detect multiple RVFV strains in FFPE tissues, enabling visual correlation of RVFV RNA presence with histopathologic lesions.
Izabela K. Ragan; Kaitlynn N. Schuck; Deepa Upreti; Lieza Odendaal; Juergen A. Richt; Jessie D. Trujillo; William Wilson; A. Sally Davis. Rift Valley Fever Viral RNA Detection by In Situ Hybridization in Formalin-Fixed, Paraffin-Embedded Tissues. Vector-Borne and Zoonotic Diseases 2019, 19, 553 -556.
AMA StyleIzabela K. Ragan, Kaitlynn N. Schuck, Deepa Upreti, Lieza Odendaal, Juergen A. Richt, Jessie D. Trujillo, William Wilson, A. Sally Davis. Rift Valley Fever Viral RNA Detection by In Situ Hybridization in Formalin-Fixed, Paraffin-Embedded Tissues. Vector-Borne and Zoonotic Diseases. 2019; 19 (7):553-556.
Chicago/Turabian StyleIzabela K. Ragan; Kaitlynn N. Schuck; Deepa Upreti; Lieza Odendaal; Juergen A. Richt; Jessie D. Trujillo; William Wilson; A. Sally Davis. 2019. "Rift Valley Fever Viral RNA Detection by In Situ Hybridization in Formalin-Fixed, Paraffin-Embedded Tissues." Vector-Borne and Zoonotic Diseases 19, no. 7: 553-556.
Rift Valley fever (RVF) is a mosquito-borne disease that affects both ruminants and humans, with epidemics occurring more frequently in recent years in Africa and the Middle East, probably as a result of climate change and intensified livestock trade. Sheep necropsied during the 2010 RVF outbreak in South Africa were examined by histopathology and immunohistochemistry (IHC). A total of 124 sheep were available for study, of which 99 cases were positive for RVF. Multifocal-random, necrotizing hepatitis was confirmed as the most distinctive lesion of RVF cases in adult sheep. Of cases where liver, spleen, and kidney tissues were available, 45 of 70 had foci of acute renal tubular epithelial injury in addition to necrosis in both the liver and spleen. In some cases, acute renal injury was the most significant RVF lesion. Immunolabeling for RVFV was most consistent and unequivocal in liver, followed by spleen, kidney, lung, and skin. RVFV antigen-positive cells included hepatocytes, adrenocortical epithelial cells, renal tubular epithelial cells, macrophages, neutrophils, epidermal keratinocytes, microvascular endothelial cells, and vascular smooth muscle. The minimum set of specimens to be submitted for histopathology and IHC to confirm or exclude a diagnosis of RVFV are liver, spleen, and kidney. Skin from areas with visible crusts and lung could be useful additional samples. In endemic areas, cases of acute renal tubular injury should be investigated further if other more common causes of renal lesions have already been excluded. RVFV can also cause an acute infection in the testis, which requires further investigation.
Lieza Odendaal; Sarah J. Clift; Geoffrey T. Fosgate; A. Sally Davis. Lesions and Cellular Tropism of Natural Rift Valley Fever Virus Infection in Adult Sheep. Veterinary Pathology 2018, 56, 61 -77.
AMA StyleLieza Odendaal, Sarah J. Clift, Geoffrey T. Fosgate, A. Sally Davis. Lesions and Cellular Tropism of Natural Rift Valley Fever Virus Infection in Adult Sheep. Veterinary Pathology. 2018; 56 (1):61-77.
Chicago/Turabian StyleLieza Odendaal; Sarah J. Clift; Geoffrey T. Fosgate; A. Sally Davis. 2018. "Lesions and Cellular Tropism of Natural Rift Valley Fever Virus Infection in Adult Sheep." Veterinary Pathology 56, no. 1: 61-77.
The NSs protein encoded by the S segment of Rift Valley fever virus (RVFV) is the major virulence factor, counteracting the host innate antiviral defence. It contains five highly conserved cysteine residues at positions 39, 40, 149, 178 and 194, which are thought to stabilize the tertiary and quaternary structure of the protein. Here, we report significant differences between clinical, virological, histopathological and host gene responses in BALB/c mice infected with wild-type RVFV (wtRVFV) or a genetic mutant having a double cysteine-to-serine substitution at residues 39 and 40 of the NSs protein (RVFV-C39S/C40S). Mice infected with the wtRVFV developed a fatal acute disease; characterized by high levels of viral replication, severe hepatocellular necrosis, and massive up-regulation of transcription of genes encoding type I and -II interferons (IFN) as well as pro-apoptotic and pro-inflammatory cytokines. The RVFV-C39S/C40S mutant did not cause clinical disease and its attenuated virulence was consistent with virological, histopathological and host gene expression findings in BALB/c mice. Clinical signs in mice infected with viruses containing cysteine-to-serine substitutions at positions 178 or 194 were similar to those occurring in mice infected with the wtRVFV, while a mutant containing a substitution at position 149 caused mild, non-fatal disease in mice. As mutant RVFV-C39S/C40S showed an attenuated phenotype in mice, the molecular mechanisms behind this attenuation were further investigated. The results show that two mechanisms are responsible for the attenuation; (1) loss of the IFN antagonistic propriety characteristic of the wtRVFV NSs and (2) the inability of the attenuated mutant to degrade Proteine Kinase R (PKR).
Gaby E.R. Monteiro; Petrus Jansen van Vuren; Paul J. Wichgers Schreur; Lieza Odendaal; Sarah J. Clift; Jeroen Kortekaas; Janusz T. Paweska. Mutation of adjacent cysteine residues in the NSs protein of Rift Valley fever virus results in loss of virulence in mice. Virus Research 2018, 249, 31 -44.
AMA StyleGaby E.R. Monteiro, Petrus Jansen van Vuren, Paul J. Wichgers Schreur, Lieza Odendaal, Sarah J. Clift, Jeroen Kortekaas, Janusz T. Paweska. Mutation of adjacent cysteine residues in the NSs protein of Rift Valley fever virus results in loss of virulence in mice. Virus Research. 2018; 249 ():31-44.
Chicago/Turabian StyleGaby E.R. Monteiro; Petrus Jansen van Vuren; Paul J. Wichgers Schreur; Lieza Odendaal; Sarah J. Clift; Jeroen Kortekaas; Janusz T. Paweska. 2018. "Mutation of adjacent cysteine residues in the NSs protein of Rift Valley fever virus results in loss of virulence in mice." Virus Research 249, no. : 31-44.
Rift Valley fever (RVF), caused by an arthropod borne Phlebovirus in the family Bunyaviridae, is a haemorrhagic disease that affects ruminants and humans. Due to the zoonotic nature of the virus, a biosafety level 3 laboratory is required for isolation of the virus. Fresh and frozen samples are the preferred sample type for isolation and acquisition of sequence data. However, these samples are scarce in addition to posing a health risk to laboratory personnel. Archived formalin-fixed, paraffin-embedded (FFPE) tissue samples are safe and readily available, however FFPE derived RNA is in most cases degraded and cross-linked in peptide bonds and it is unknown whether the sample type would be suitable as reference material for retrospective phylogenetic studies. A RT-PCR assay targeting a 490 nt portion of the structural GN glycoprotein encoding gene of the RVFV M-segment was applied to total RNA extracted from archived RVFV positive FFPE samples. Several attempts to obtain target amplicons were unsuccessful. FFPE samples were then analysed using next generation sequencing (NGS), i.e. Truseq® (Illumina) and sequenced on the Miseq® genome analyser (Illumina). Using reference mapping, gapped virus sequence data of varying degrees of shallow depth was aligned to a reference sequence. However, the NGS did not yield long enough contigs that consistently covered the same genome regions in all samples to allow phylogenetic analysis.
B. Mubemba; Peter Thompson; L. Odendaal; P. Coetzee; E.H. Venter. Evaluation of positive Rift Valley fever virus formalin-fixed paraffin embedded samples as a source of sequence data for retrospective phylogenetic analysis. Journal of Virological Methods 2017, 243, 10 -14.
AMA StyleB. Mubemba, Peter Thompson, L. Odendaal, P. Coetzee, E.H. Venter. Evaluation of positive Rift Valley fever virus formalin-fixed paraffin embedded samples as a source of sequence data for retrospective phylogenetic analysis. Journal of Virological Methods. 2017; 243 ():10-14.
Chicago/Turabian StyleB. Mubemba; Peter Thompson; L. Odendaal; P. Coetzee; E.H. Venter. 2017. "Evaluation of positive Rift Valley fever virus formalin-fixed paraffin embedded samples as a source of sequence data for retrospective phylogenetic analysis." Journal of Virological Methods 243, no. : 10-14.
Egyptian fruit bats (Rousettus aegyptiacus) were inoculated subcutaneously (n = 22) with Marburg virus (MARV). No deaths, overt signs of morbidity, or gross lesions was identified, but microscopic pathological changes were seen in the liver of infected bats. The virus was detected in 15 different tissues and plasma but only sporadically in mucosal swab samples, urine, and fecal samples. Neither seroconversion nor viremia could be demonstrated in any of the in-contact susceptible bats (n = 14) up to 42 days after exposure to infected bats. In bats rechallenged (n = 4) on day 48 after infection, there was no viremia, and the virus could not be isolated from any of the tissues tested. This study confirmed that infection profiles are consistent with MARV replication in a reservoir host but failed to demonstrate MARV transmission through direct physical contact or indirectly via air. Bats develop strong protective immunity after infection with MARV.
Janusz T. Paweska; Petrus Jansen Van Vuren; Karla A. Fenton; Kerry Graves; Antoinette A. Grobbelaar; Naazneen Moolla; Patricia Leman; Jacqueline Weyer; Nadia Storm; Stewart D. McCulloch; Terence Scott; Wanda Markotter; Lieza Odendaal; Sarah J. Clift; Thomas W. Geisbert; Martin J. Hale; Alan Kemp. Lack of Marburg Virus Transmission From Experimentally Infected to Susceptible In-Contact Egyptian Fruit Bats. Journal of Infectious Diseases 2015, 212, S109 -S118.
AMA StyleJanusz T. Paweska, Petrus Jansen Van Vuren, Karla A. Fenton, Kerry Graves, Antoinette A. Grobbelaar, Naazneen Moolla, Patricia Leman, Jacqueline Weyer, Nadia Storm, Stewart D. McCulloch, Terence Scott, Wanda Markotter, Lieza Odendaal, Sarah J. Clift, Thomas W. Geisbert, Martin J. Hale, Alan Kemp. Lack of Marburg Virus Transmission From Experimentally Infected to Susceptible In-Contact Egyptian Fruit Bats. Journal of Infectious Diseases. 2015; 212 (suppl 2):S109-S118.
Chicago/Turabian StyleJanusz T. Paweska; Petrus Jansen Van Vuren; Karla A. Fenton; Kerry Graves; Antoinette A. Grobbelaar; Naazneen Moolla; Patricia Leman; Jacqueline Weyer; Nadia Storm; Stewart D. McCulloch; Terence Scott; Wanda Markotter; Lieza Odendaal; Sarah J. Clift; Thomas W. Geisbert; Martin J. Hale; Alan Kemp. 2015. "Lack of Marburg Virus Transmission From Experimentally Infected to Susceptible In-Contact Egyptian Fruit Bats." Journal of Infectious Diseases 212, no. suppl 2: S109-S118.
Real-time reverse transcription polymerase chain reaction (real-time RT-PCR), histopathology, and immunohistochemical labeling (IHC) were performed on liver specimens from 380 naturally infected cattle and sheep necropsied during the 2010 Rift Valley fever (RVF) epidemic in South Africa. Sensitivity (Se) and specificity (Sp) of real-time RT-PCR, histopathology, and IHC were estimated in a latent-class model using a Bayesian framework. The Se and Sp of real-time RT-PCR were estimated as 97.4% (95% confidence interval [CI] = 95.2–98.8%) and 71.7% (95% CI = 65–77.9%) respectively. The Se and Sp of histopathology were estimated as 94.6% (95% CI = 91–97.2%) and 92.3% (95% CI = 87.6–95.8%), respectively. The Se and Sp of IHC were estimated as 97.6% (95% CI = 93.9–99.8%) and 99.4% (95% CI = 96.9–100%), respectively. Decreased Sp of real-time RT-PCR was ascribed to cross-contamination of samples. Stratified analysis of the data suggested variations in test accuracy with fetuses and severely autolyzed specimens. The Sp of histopathology in fetuses (83%) was 9.3% lower than the sample population (92.3%). The Se of IHC decreased from 97.6% to 81.5% in the presence of severe autolysis. The diagnostic Se and Sp of histopathology was higher than expected, confirming the value of routine postmortem examinations and histopathology of liver specimens. Aborted fetuses, however, should be screened using a variety of tests in areas endemic for RVF, and results from severely autolyzed specimens should be interpreted with caution. The most feasible testing option for countries lacking suitably equipped laboratories seems to be routine histology in combination with IHC.
Lieza Odendaal; Geoffrey T. Fosgate; Marco Romito; Jacobus A. W. Coetzer; Sarah J. Clift. Sensitivity and specificity of real-time reverse transcription polymerase chain reaction, histopathology, and immunohistochemical labeling for the detection of Rift Valley fever virus in naturally infected cattle and sheep. Journal of Veterinary Diagnostic Investigation 2014, 26, 49 -60.
AMA StyleLieza Odendaal, Geoffrey T. Fosgate, Marco Romito, Jacobus A. W. Coetzer, Sarah J. Clift. Sensitivity and specificity of real-time reverse transcription polymerase chain reaction, histopathology, and immunohistochemical labeling for the detection of Rift Valley fever virus in naturally infected cattle and sheep. Journal of Veterinary Diagnostic Investigation. 2014; 26 (1):49-60.
Chicago/Turabian StyleLieza Odendaal; Geoffrey T. Fosgate; Marco Romito; Jacobus A. W. Coetzer; Sarah J. Clift. 2014. "Sensitivity and specificity of real-time reverse transcription polymerase chain reaction, histopathology, and immunohistochemical labeling for the detection of Rift Valley fever virus in naturally infected cattle and sheep." Journal of Veterinary Diagnostic Investigation 26, no. 1: 49-60.
Eosinophilic meningoencephalitis (EME) has been described in various species of animals and in humans. In dogs it has been associated with protozoal infections, cuterebral myiasis and various other aetiologies. Ten cases of idiopathic eosinophilic meningoencephalitis have been reported in dogs and one in a cat where the origin was uncertain or unknown. The dogs were all males, of various breeds but with a predominance of Golden Retrievers and Rottweilers; they generally had a young age of onset. Two cases with no apparent underlying aetiology were diagnosed on post mortem examination. The 18-month-old, male Boerboel presented with sudden onset of cerebellar ataxia, as well as various asymmetrical cranial nerve deficits of 2 weeks' duration and without progression. Haematology revealed a peripheral eosinophilia. Necropsy showed extreme generalised congestion especially of the meninges and blood smear and histological sections of various tissues showed intravascular erythrocyte fragmentation with the formation of microcytes. Histopathology revealed severe diffuse cerebrocortical subarachnoidal meningitis and submeningeal encephalitis, the exudate containing variable numbers of eosinophils together with neutrophils and mononuclear cells. There was also deeper white matter and hippocampal multifocal perivascular mononuclear encephalitis and multifocal periventricular malacia, gliosis and phagocytosis of white matter. The cerebellum, brain stem and spinal cord showed only mild multifocal oedema or scattered occasional axon and myelin degeneration respectively, with no inflammation. Immunohistochemical staining of central nervous tissue for Toxoplasma gondii failed to show any antigen in the central nervous tissue. Ultrastructure of a single submeningeal suspected parasitic cyst showed it to be chromatin clumping within a neuron nucleus indicating karyorrhexis. Gram stain provided no evidence of an aetiological agent. The 3-year-old Beagle bitch had a Caesarian section after developing a non-responsive inertia 8 days prior to presentation. This animal's clinical signs included status epilepticus seizures unrelated to hypocalcaemia and warranted induction of a barbiturate coma. She died 4 hours later. Post mortem and histopathological findings in the brain were almost identical to those of the Boerboel and she also showed histological evidence of recent active intravascular haemolysis with microcyte formation. Rabies, distemper and Neospora caninum immunohistochemical stains were negative in the brains of both dogs. Immunohistochemical staining of the cerebral and meningeal exudates of the Beagle for T- and B-lymphocyte (CD3 and CD79a) markers showed a predominance of T-lymphocytes with fewer scattered B lymphocytes. A possible allergic response to amoxicillin / clavulanate is considered, as this appeared to be the only feature common to the recent history of both animals. An overview of EME in humans, dogs and cats is given and the previously published cases of idiopathic EME in dogs and the single published cat case are briefly reviewed.
J.H. Williams; Liza Koster; V. Naidoo; Lieza Odendaal; A. Van Veenhuysen; M. De Wit; E. Van Wilpe. Review of idiopathic eosinophilic meningitis in dogs and cats, with a detailed description of two recent cases in dogs : review and clinical communication. Journal of the South African Veterinary Association 2008, 79, 194-204 -204.
AMA StyleJ.H. Williams, Liza Koster, V. Naidoo, Lieza Odendaal, A. Van Veenhuysen, M. De Wit, E. Van Wilpe. Review of idiopathic eosinophilic meningitis in dogs and cats, with a detailed description of two recent cases in dogs : review and clinical communication. Journal of the South African Veterinary Association. 2008; 79 (4):194-204-204.
Chicago/Turabian StyleJ.H. Williams; Liza Koster; V. Naidoo; Lieza Odendaal; A. Van Veenhuysen; M. De Wit; E. Van Wilpe. 2008. "Review of idiopathic eosinophilic meningitis in dogs and cats, with a detailed description of two recent cases in dogs : review and clinical communication." Journal of the South African Veterinary Association 79, no. 4: 194-204-204.