Increased Susceptibility of Cattle to Intranasal RVFV Infection

Abstract

Rift Valley Fever virus (RVFV) is a zoonotic mosquito-borne virus that belongs to the Phenuiviridae family. Infections in animal herds cause abortion storms, high mortality rates in neonates, and mild to severe symptoms. Infected animals can also transmit the virus to people, particularly people who live or work in close contact with livestock. There is currently an ongoing effort to produce safe and efficacious veterinary vaccines against RVFV in livestock to protect against both primary infection in animals and zoonotic infections in people. To test the efficacy of these vaccines it is essential to have a reliable challenge model in relevant target species, including ruminants. In this study we evaluated three routes of inoculation (intranasal, intradermal and a combination of routes) in Holstein cattle using an infectious dose of 10 7 pfu/ml and a virus strain from the 2006-2007 outbreak in Kenya and Sudan. Our results demonstrated that all routes of inoculation were effective at producing viremia in all animals; however, the intranasal route induced the highest levels and longest duration of viremia, the most noticeable clinical signs, and the most widespread infection of tissues. We therefore recommend using the intranasal inoculation for future vaccine and challenge studies.

Degenerate sequence-based CRISPR diagnostic for Crimean–Congo hemorrhagic fever virus

“…CCHFV IbAr10200 was a kind gift from David Safronetz (Public Health Agency of Canada) and Heinz Feldmann (Then Public Health Agency of Canada) [43,44]. SW13 (Scott and White [47,48]. TriPure-inactivated samples as prepared above were extracted for viral RNA using the MagMAX CORE Nucleic Acid Purification Kit (ThermoFisher Scientific, A32700) on a KingFisher magnetic particle processor (ThermoFisher Scientific, A31508).…”

Livestock Challenge Models of Rift Valley Fever for Agricultural Vaccine Testing

“…All three routes of infection all produced viremia in all animals as well as mild but observable clinical signs such as fever, a depressed disposition, and a lessened appetite in some animals (Supplementary Figure 1). Viral RNA was detected in nasal swabs but no infectious virus was present (126).…”

“…Our results indicated that the degree of viremia was similar to that of a subcutaneous infection, although far fewer tissues tested positive for virus presence in the intradermal model. After intradermal inoculation, infectious virus was only found in turbinates, prescapular lymph nodes, and retropharyngeal lymph nodes (126). Although ruminants are not known to become infected intranasally in the wild, they are quite susceptible to intranasal infection.…”

“…Although ruminants are not known to become infected intranasally in the wild, they are quite susceptible to intranasal infection. Intranasal inoculation of cattle led to high titers of viremia with peak titers of 6 × 10 5 pfu/ml blood and produced infectious virus in a variety of tissues including spleen, liver, kidney, lymph nodes, heart, thyroid, turbinates, and cerebellum (126). We speculated that during intranasal and subcutaneous/intradermal RVFV inoculations, the virus may follow different pathways to reach the bloodstream (117).…”

“…All young ruminants (<3 months) are highly susceptible to RVFV infection and typically succumb to acute liver failure (89,(135)(136)(137). Recent studies at KSU and NCFAD have opted to develop challenge models in animals old enough to be weaned (4-6 months) due to the logistics of working in high containment (112,113,117,125,126 (82). The first RVFV strain was Buffalo/99/MB/CER, isolated from an aborted fetus from an outbreak in 1998, and the second strain was the reference strain RVF 35-74, isolated from a sick sheep from an outbreak in 1974.…”