Particle-to-PFU Ratio of Ebola Virus Influences Disease Course and Survival in Cynomolgus Macaques

Alfson, Kendra J.; Avena, Laura E.; Beadles, Michael W.; Staples, Hilary; Nunneley, Jerritt; Ticer, Anysha; Dick, Edward J.; Owston, Michael A.; Reed, Christopher; Patterson, Jean L.; Carrión, Ricardo; Griffiths, Anthony John

doi:10.1128/jvi.00649-15

Cited by 58 publications

(95 citation statements)

References 32 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The current study used a virus stock produced by a single amplification of the clinical sample on cultured cells for the Makona EBOV isolates, as opposed to at least 2 amplification rounds on cultured cells for the other studies [9][10][11][12]. A past study showed that multiple rounds of EBOV amplification on cultured cells was associated with decreased virus potency in a lethal cynomolgus macaque model of infection [26].…”

Section: Discussionmentioning

confidence: 99%

Pathogenicity Comparison Between the Kikwit and Makona Ebola Virus Variants in Rhesus Macaques

et al. 2016

View full text Add to dashboard Cite

Enhanced virulence and/or transmission of West African Ebola virus (EBOV) variants, which are divergent from their Central African counterparts, are suspected to have contributed to the sizable toll of the recent Ebola virus disease (EVD) outbreak. This study evaluated the pathogenicity and shedding in rhesus macaques infected with 1 of 2 West African isolates (EBOV-C05 or EBOV-C07) or a Central African isolate (EBOV-K). All animals infected with EBOV-C05 or EBOV-C07 died of EVD, whereas 2 of 3 EBOV-Kinfected animals died. The viremia level was elevated 10-fold in EBOV-C05-infected animals, compared with EBOV-C07-or EBOV-K-infected animals. More-severe lung pathology was observed in 2 of 6 EBOV-C05/C07-infected macaques. This is the first detailed analysis of the recently circulating EBOV-C05/C07 in direct comparison to EBOV-K with 6 animals per group, and it showed that EBOV-C05 but not EBOV-C07 can replicate at higher levels and cause more tissue damage in some animals. Increased virus shedding from individuals who are especially susceptible to EBOV replication is possibly one of the many challenges facing the community of healthcare and policy-making responders since the beginning of the outbreak.

show abstract

Section: Discussionmentioning

confidence: 99%

Pathogenicity Comparison Between the Kikwit and Makona Ebola Virus Variants in Rhesus Macaques

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In animal models, Ebola virus transmission has been demonstrated through direct virus inoculation in mucosa (via the oral or conjunctival route); subcutaneous, intraperitoneal, or intramuscular injection; and via the respiratory tract, through respiratory droplets and aerosols. Small viral inocula of <1 plaque-forming unit can be infectious [45]. Inoculation of the conjunctiva or oropharyngeal mucosa, as well as transcutaneous infection via tiny skin breaches, are considered the main routes of natural transmission in humans.…”

Section: Transmissionmentioning

confidence: 99%

Ebola Virus Shedding and Transmission: Review of Current Evidence

et al. 2016

View full text Add to dashboard Cite

Background. The magnitude of the 2013-2016 Ebola virus disease outbreak in West Africa was unprecedented, with >28 500 reported cases and >11 000 deaths. Understanding the key elements of Ebola virus transmission is necessary to implement adequate infection prevention and control measures to protect healthcare workers and halt transmission in the community.Methods. We performed an extensive PubMed literature review encompassing the period from discovery of Ebola virus, in 1976, until 1 June 2016 to evaluate the evidence on modes of Ebola virus shedding and transmission.Findings. Ebola virus has been isolated by cell culture from blood, saliva, urine, aqueous humor, semen, and breast milk from infected or convalescent patients. Ebola virus RNA has been noted in the following body fluids days or months after onset of illness: saliva (22 days), conjunctiva/tears (28 days), stool (29 days), vaginal fluid (33 days), sweat (44 days), urine (64 days), amniotic fluid (38 days), aqueous humor (101 days), cerebrospinal fluid (9 months), breast milk (16 months [ preliminary data]), and semen (18 months). Nevertheless, the only documented cases of secondary transmission from recovered patients have been through sexual transmission. We did not find strong evidence supporting respiratory or fomite-associated transmission.

show abstract

“…Alfson et al . () have demonstrated EBOV virus particle‐to‐PFU ratios of up to 10 4 –10 5 which decreased to ~10 3 after multiple passage in cell culture as the virions became better adapted to forming plaques. It is interesting to note that filoviruses are unusual in being filamentous animal viruses.…”

Section: The Effect Of Passaging In a Host Species On The Dose–responmentioning

confidence: 99%

“…This is supported by the work of Alfson et al . () which showed that EBOV stocks with high particle‐to‐PFU ratios (and isolated after only a few passages in cell culture) contained virus particles that were able to cause lethal disease in NHPs (macaques) but were not able to generate plaques in Vero cell culture. Indeed there is an inverse relationship between EBOV infectivity in animals and the ability to form plaques in cell culture.…”

Section: The Effect Of Passaging In a Host Species On The Dose–responmentioning

confidence: 99%

See 1 more Smart Citation

The challenge of using experimental infectivity data in risk assessment for Ebola virus: why ecology may be important

et al. 2015

View full text Add to dashboard Cite

SummaryAnalysis of published data shows that experimental passaging of Zaire ebolavirus (EBOV) in guinea pigs changes the risk of infection per plaqueforming unit (PFU), increasing infectivity to some species while decreasing infectivity to others. Thus, a PFU of monkey-adapted EBOV is 10 7 -fold more lethal to mice than a PFU adapted to guinea pigs. The first conclusion is that the infectivity of EBOV to humans may depend on the identity of the donor species itself and, on the basis of limited epidemiological data, the question is raised as to whether bat-adapted EBOV is less infectious to humans than nonhuman primate (NHP)-adapted EBOV. Wildlife species such as bats, duikers and NHPs are naturally infected by EBOV through different species giving rise to EBOV with different wildlife species-passage histories (heritages). Based on the ecology of these wildlife species, three broad 'types' of EBOVinfected bushmeat are postulated reflecting differences in the number of passages within a given species, and hence the degree of adaptation of the EBOV present. The second conclusion is that the prior species-transmission chain may affect the infectivity to humans per PFU for EBOV from individuals of the same species. This is supported by the finding that the related Marburg marburgvirus requires ten passages in mice to fully adapt. It is even possible that the evolutionary trajectory of EBOV could vary in individuals of the same species giving rise to variants which are more or less virulent to humans and that the probability of a given trajectory is related to the heritage. Overall the ecology of the donor species (e.g. dog or bushmeat species) at the level of the individual animal itself may determine the risk of infection per PFU to humans reflecting the heritage of the virus and may contribute to the sporadic nature of EBOV outbreaks.

show abstract

Particle-to-PFU Ratio of Ebola Virus Influences Disease Course and Survival in Cynomolgus Macaques

Cited by 58 publications

References 32 publications

Pathogenicity Comparison Between the Kikwit and Makona Ebola Virus Variants in Rhesus Macaques

Pathogenicity Comparison Between the Kikwit and Makona Ebola Virus Variants in Rhesus Macaques

Ebola Virus Shedding and Transmission: Review of Current Evidence

The challenge of using experimental infectivity data in risk assessment for Ebola virus: why ecology may be important

Contact Info

Product

Resources

About