Experimental Infection of Dogs and Monkeys with Two Rabies Serogroup Viruses, Lagos Bat and Mokola (IbAn 27377). Gross Pathologic and Histopathologic Changes

Percy, D. H.; Bhatt, P. N.; Tignor, Gregory H.; Shope, Robert E.

doi:10.1177/030098587301000607

Cited by 15 publications

(12 citation statements)

References 18 publications

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“…Second, rMOKV is not pathogenic by the i.m. route ( Figure S4 ), consistent with WT MOKV studies ( Badrane et al., 2001 ; Percy et al., 1973 ; Perrin et al., 1996 ). Third, the i.n.…”

Section: Discussionsupporting

confidence: 87%

Lyssavirus Vaccine with a Chimeric Glycoprotein Protects across Phylogroups

Fisher¹,

Lowe²,

Smith³

et al. 2020

Cell Reports

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Summary Rabies is nearly 100% lethal in the absence of treatment, killing an estimated 59,000 people annually. Vaccines and biologics are highly efficacious when administered properly. Sixteen rabies-related viruses (lyssaviruses) are similarly lethal, but some are divergent enough to evade protection from current vaccines and biologics, which are based only on the classical rabies virus (RABV). Here we present the development and characterization of LyssaVax, a vaccine featuring a structurally designed, functional chimeric glycoprotein (G) containing immunologically important domains from both RABV G and the highly divergent Mokola virus (MOKV) G. LyssaVax elicits high titers of antibodies specific to both RABV and MOKV Gs in mice. Immune sera also neutralize a range of wild-type lyssaviruses across the major phylogroups. LyssaVax-immunized mice are protected against challenge with recombinant RABV and MOKV. Altogether, LyssaVax demonstrates the utility of structural modeling in vaccine design and constitutes a broadened lyssavirus vaccine candidate.

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“…Second, rMOKV is not pathogenic by the i.m. route ( Figure S4 ), consistent with WT MOKV studies ( Badrane et al., 2001 ; Percy et al., 1973 ; Perrin et al., 1996 ). Third, the i.n.…”

Section: Discussionsupporting

confidence: 87%

Lyssavirus Vaccine with a Chimeric Glycoprotein Protects across Phylogroups

Fisher¹,

Lowe²,

Smith³

et al. 2020

Cell Reports

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“…Lymphocytic retinal inflammation has been demonstrated following experimental rabies virus infection in dogs and mice. 6,27 While the retinal inflammation associated with rabies and other neurotropic viral infections typically reflects the lymphocytic and plasmacytic inflammation present in the CNS, 34 our results revealed a minimal and predominantly T-cell response throughout the examined cases, with no B-cell component within inflammatory infiltrates. A lack of B-cell response has been occasionally found in cases of rabies and other viral infections of the eye.…”

Section: Discussionmentioning

confidence: 63%

“…16 A few reports investigating the extraneural changes associated with experimental rabies virus infection in rabbits, hamsters, dogs, monkeys, foxes, and skunks have revealed similar inflammatory and degenerative lesions in the eye of infected animals. 3,9,10,26,27 However, no studies have focused on the ocular and lacrimal gland lesions caused by naturally occurring rabies in domestic and wild animals. Here we describe the pathological changes in the eye, optic nerve, and lacrimal gland in domestic and wild mammals submitted for diagnosis of rabies and compare different diagnostic methods using frozen and formalin-fixed tissues from affected animals.…”

mentioning

confidence: 99%

Ocular and Lacrimal Gland Lesions in Naturally Occurring Rabies of Domestic and Wild Mammals

et al. 2020

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Investigations describing the ocular and lacrimal gland lesions associated with rabies are sparse. Here we characterize the pathological changes and distribution of rabies viral antigen in the eye, optic nerve, and lacrimal gland of 18 rabies cases from different mammalian species. Histology and immunohistochemistry for rabies virus, CD3, CD20, and Iba1 were performed on tissue sections of eye, optic nerve, and lacrimal gland. Polymerase chain reaction (PCR) for rabies was performed on all cases, including 7 formalin-fixed, paraffin-embedded (FFPE) and 11 frozen tissue samples of eye and lacrimal gland. Pathological changes in the eye consisted of retinal necrosis (12/18 cases) with occasional viral inclusions within ganglion cells (8/12 cases). Immunohistochemically, viral antigen was detected within the nerve fiber layer, ganglion cells, and inner plexiform layer in all 12 cases with retinal lesions and in 2 cases with no retinal lesions, as well as optic nerve (6/18 cases) and lacrimal gland epithelium (3/18 cases). CD3+ T lymphocytes were present in the retina (11/18 cases), optic nerve (2/18 cases), and lacrimal gland (11/18 cases). No CD20+ B lymphocytes or Iba1+ macrophages were detected. PCR for rabies virus was positive in 9 of 11 frozen samples but in only 2 of 7 FFPE samples. Five samples that were negative for rabies by PCR were positive by immunohistochemistry, and 2 samples were negative by both tests. These results provide evidence that rabies virus infection extends to the eye, likely via the ocular nerve, and that the lacrimal gland might be a source of viral infection.

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“…All three strains originally had been isolated from the brains of straw-colored fruit bats [ 47 – 49 ]. These strains differ in passage history and ability to cause infection in laboratory animals [ 11 , 50 – 54 ]. To determine their ability to cause in vivo infection in a reservoir species, we inoculated these LBV strains into the cerebrum of straw-colored fruit bats.…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis of bat rabies in a natural reservoir: Comparative susceptibility of the straw-colored fruit bat (Eidolon helvum) to three strains of Lagos bat virus

et al. 2018

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Rabies is a fatal neurologic disease caused by lyssavirus infection. People are infected through contact with infected animals. The relative increase of human rabies acquired from bats calls for a better understanding of lyssavirus infections in their natural hosts. So far, there is no experimental model that mimics natural lyssavirus infection in the reservoir bat species. Lagos bat virus is a lyssavirus that is endemic in straw-colored fruit bats (Eidolon helvum) in Africa. Here we compared the susceptibility of these bats to three strains of Lagos bat virus (from Senegal, Nigeria, and Ghana) by intracranial inoculation. To allow comparison between strains, we ensured the same titer of virus was inoculated in the same location of the brain of each bat. All bats (n = 3 per strain) were infected, and developed neurological signs, and fatal meningoencephalitis with lyssavirus antigen expression in neurons. There were three main differences among the groups. First, time to death was substantially shorter in the Senegal and Ghana groups (4 to 6 days) than in the Nigeria group (8 days). Second, each virus strain produced a distinct clinical syndrome. Third, the spread of virus to peripheral tissues, tested by hemi-nested reverse transcriptase PCR, was frequent (3 of 3 bats) and widespread (8 to 10 tissues positive of 11 tissues examined) in the Ghana group, was frequent and less widespread in the Senegal group (3/3 bats, 3 to 6 tissues positive), and was rare and restricted in the Nigeria group (1/3 bats, 2 tissues positive). Centrifugal spread of virus from brain to tissue of excretion in the oral cavity is required to enable lyssavirus transmission. Therefore, the Senegal and Ghana strains seem most suitable for further pathogenesis, and for transmission, studies in the straw-colored fruit bat.

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Experimental Infection of Dogs and Monkeys with Two Rabies Serogroup Viruses, Lagos Bat and Mokola (IbAn 27377). Gross Pathologic and Histopathologic Changes

Cited by 15 publications

References 18 publications

Lyssavirus Vaccine with a Chimeric Glycoprotein Protects across Phylogroups

Lyssavirus Vaccine with a Chimeric Glycoprotein Protects across Phylogroups

Ocular and Lacrimal Gland Lesions in Naturally Occurring Rabies of Domestic and Wild Mammals

Pathogenesis of bat rabies in a natural reservoir: Comparative susceptibility of the straw-colored fruit bat (Eidolon helvum) to three strains of Lagos bat virus

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