Palyam serogroup orbivirus infections

Previous author: R SWANEPOEL

Current author: M QUAN, PhD, Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, South Africa

GENERAL INTRODUCTION: REOVIRIDAE

Introduction

Palyam serogroup orbiviruses are arthropod-borne viruses that occur in Africa, Asia and Australia, and which appear to be associated with abortion and teratology in cattle and possibly other ruminants.

At present, 13 viruses are recognized as members of the serogroup. The original members, Palyam, Kasba and Vellore viruses, were isolated from mosquitoes in southern India in 1956, 1957 and 1966 in the course of investigation of Japanese encephalitis.^{6, 7, 8, 33} Many of the remaining members were also obtained initially from haematophagous arthropods (Table 1).

The first indication that the members of the Palyam serogroup may be pathogenic was provided by the isolation of Nyabira, Gweru and Abadina viruses from aborted cattle foetuses in Zimbabwe^{38, 39, 43} and the detection of antibodies to Nyabira virus in the sera of aborted foetuses.³⁷ Antibodies to Nyabira virus were found to be widely distributed in cattle sera in Zimbabwe, and rising titres or seroconversions were recorded on occasion in heifers and cows that aborted.^{2, 37, 38}

At least five serotypes of the group, Abadina, Nyabira, Gweru, Marondera and Apies River viruses (Table 1), are known to occur in southern Africa,^{43, 46} but further isolates from aborted cattle foetuses in Zimbabwe, and from Culicoides midges and aborted sheep foetuses in South Africa, have not been typed.^{12, 15, 36} Neutralizing antibodies to one or more of the five known serotypes were found in the sera of cattle, sheep, goats and humans collected at ten widely separated locations in South Africa, with the prevalence of antibodies being much higher in cattle (53,4 per cent) than in the other species (4 to 14,1 per cent).⁴⁶

In Japan, an epidemic of congenital abnormalities in cattle was noted in Kyushu district between November 1987 and April 1988, with at least 2 463 calves affected by hydranencephaly and cerebellar hypoplasia.^{16, 17} A Palyam serogroup virus, initially given the name Chuzan, was incriminated as the causative agent of the outbreak in epidemiological studies, which included demonstration of antibodies in pre-colostral sera of affected calves and pathogenicity tests. ^{16, 17, 29, 30, 31} Subsequently, it was found that Chuzan virus was the same as Kagoshima virus, which had previously been isolated from midges in Japan, and later both viruses were found to be the same as Kasba virus, which had originally been isolated in India.^{23, 27}

There have been over 100 isolations of Palyam serogroup viruses from blood samples of sentinel cattle in Australia, yaks in China and antibodies to the viruses have been demonstrated in the sera of cattle and Asian buffaloes in Australia, cattle in India and Nigeria, and goats in South Korea, all in the absence of evidence of disease.^{5, 14, 32, 33, 40, 41}

Aetiology

Palyam serogroup viruses have morphological and physicochemical properties typical of members of the genus Orbivirus of the family Reoviridae ^{3, 21, 25, 26, 27, 42, 44, 47, 48} (see Bluetongue, and African horse sickness). They are most closely related to African horse sickness virus and can be divided into two clades: an Afrotropical clade containing all the viruses isolated in Africa (except for Petovo virus) and another clade containing the Australasian and Oriental serotypes (and Petovo virus), with Palyam virus as the ancestor to this group.¹¹  

The viruses of the Palyam serogroup synthesize at least seven structural and four non-structural proteins during virus replication.¹¹ Virus protein (VP) 2 and VP5 constitute the outer capsid layer and have a variable antigenic structure that is specific to individual serotypes and responsible for inducing a protective immune response. The inter-relationships of the core proteins are poorly understood, but they tend to have a conserved antigenic structure that is cross-reactive within the serogroup.^{11, 42} The viruses are strongly cross-reactive in complement fixation and immunofluorescence tests, and although by definition serotypes react specifically in neutralization tests, there is some cross-reaction between closely related viruses. On this basis the members of the serogroup have been placed in six antigenic complexes.^{26, 43} (Table 2)

As with other orbiviruses, the genome of the Palyam serogroup viruses consists of ten discrete segments of double stranded RNA, with a total molecular weight of 11 to 11,5 × 10⁶. ^{26, 42} Little is known of viral attachment to susceptible cells and internalization, but replication occurs in the cytoplasm of infected cells and virus appears to be released by cell lysis.

The viruses of the serogroup are less resistant than reoviruses to lipid solvents,³⁸ remain infective for at least a period of days at ambient temperature and are very stable at temperatures below –60°C. By analogy with other orbiviruses, it can be assumed that the infectivity of the Palyam serogroup viruses is unstable below pH 6,0 and is destroyed at temperatures above 60°C. Salt- and pH-dependent haemagglutination has been demonstrated with Kasba virus.²²

Table 1 Palyam serogroup orbiviruses showing original source and year of initial isolation of each serotype

* Viruses not recognised as serotypes/strains by the International Committee on Taxonomy of Viruses (2019). Marondera virus is closely related to Apies river virus.¹¹

Table 2 The six antigenic complexes of the Palyam serogoup of orbiviruses

The Palyam serogroup viruses can be grown in mosquito cells and a wide variety of mammalian cell cultures, but primary calf testis, Vero, BHK21 and a line of hamster lung cells, HmLu-1, have been used most commonly.^{7, 18, 19, 21, 26, 27, 29, 30, 31, 39, 43} It is usually necessary to adapt the viruses by passaging them in cell cultures to obtain titratable cytopathic effect,³⁸ but infectivity can also be titrated by plaque production or demonstration of immunofluorescence in infected cells.^{20, 26, 43} The viruses can be isolated and titrated by intracerebral inoculation of suckling mice, and they cause embryonic death or teratology in embryonated chicken eggs.^{38, 45}

Epidemiology

Although two Palyam serogroup viruses were isolated from ixodid ticks (Table 1), and several others have been isolated from mosquitoes, the majority of isolations from arthropods have come from Culicoides midges.^{2, 5, 6, 9, 27, 28, 29, 46}Among the viruses known to occur in southern Africa, Abadina virus was isolated 45 times from midges and once from mosquitoes in Nigeria, while there have been five confirmed isolations of Nyabira and Gweru viruses from midges in Zimbabwe and South Africa, and 14 isolations of incompletely characterized Palyam serogroup viruses from midges in South Africa.^{2, 12, 28, 46} Transmission of the viruses by midges has not been demonstrated, but it has been shown that Nyabira virus replicates in inoculated midges.⁴ Thus, the indications are that Culicoides midges are the natural vectors of the Palyam serogroup viruses, at least in southern Africa. No vertebrate hosts for the Palyam serogroup viruses are known, apart from sheep, cattle and yaks, although antibodies have been found in Asian buffalo in Australia, and in goats and humans in South Africa and South Korea.^{5, 41, 46, 50}

Pathogenesis

Little is known of the pathogenesis of disease by Palyam serogroup viruses in non-pregnant cattle except that Kasba virus produced transient leukopaenia and viraemia without fever following intravenous inoculation.³⁰ Viraemia was demonstrable consistently for up to two weeks and then intermittently for up to eight weeks in intravenously inoculated cattle, with a maximum intensity of 10^3,5 tissue culture infective doses₅₀/ml.^{30, 31} Infective titres were higher in erythrocyte fractions of blood than in plasma.

Two calves inoculated intracerebrally showed fever and malaise from the day after inoculation and developed opisthotonus, stiff gait, tremors and nystagmus before becoming moribund six and seven days after inoculation.³⁰ Virus was recovered from brain tissue.

Fourteen out of 15 pregnant cows inoculated intravenously with Kasba virus at 89 to 150 days of gestation gave birth to normal calves, with one calf having antibody to the virus in pre-colostral serum, while the remaining cow, inoculated on Day 120 of gestation, gave birth to a calf with the hydranencephaly-cerebellar hypoplasia syndrome and antibody to the virus in its serum.³¹ Routine examination of aborted cattle foetuses in Zimbabwe failed to reveal lesions which would explain the mechanism of abortigenesis by the Palyam serogroup viruses,¹³ but variation in the occurrence of either abortion or teratology may be related to differences in timing of infection relative to the stage of gestation, or to differences in the virulence of the strains of virus involved.⁴⁵

Clinical signs and pathology

Although leukopaenia, viraemia and possibly mild fever may be recorded in Palyam serogroup infections if sentinel cattle are monitored, the occurrence of infection is usually only apparent after the event when abortion or teratology is observed. Cases of abortion or teratology may be sporadic or occur in epidemics involving one or more herds over a period of one to two weeks, or even several months.^{16, 17, 37} Abortions are most likely to occur in late summer or early autumn in southern Africa. Palyam serogroup viruses were isolated from foetuses aborted in mid- to late pregnancy in Zimbabwe, but abortions may well occur at any stage of gestation since it was unusual to receive early foetuses for examination. Retained placenta was reported to be a common complication to abortion in some of the herds where Palyam serogroup viruses were isolated from aborted foetuses.

No noteworthy macroscopic lesions were observed in aborted foetuses from which Palyam serogroup viruses were isolated in Zimbabwe, and the only consistent histopathological finding was lymphocytic infiltration in lung interstitium and portal tracts of the liver.¹³ Opisthotonus, impaired mobility, inability to suckle, hydranencephaly and cerebellar hypoplasia were common findings in calves in the epidemic associated with Kasba virus in Japan,^{16, 17} but it is possible that other congenital defects commonly found in association with brain teratology in ruminants, also occur in Palyam serogroup infections.

Diagnosis, differential diagnosis and control

Infection with Palyam serogroup viruses should be suspected when sporadic cases or epidemics of abortion and/or teratology occur in cattle or other domestic ruminants, in the absence of other overt signs of disease. Suspicion would be increased by exclusion of other known diseases causing abortion such as brucellosis, leptospirosis, chlamydiosis, salmonellosis, Rift Valley fever and Wesselsbron disease, or causes of teratology such as the Simbu serogroup orthobunyaviruses, and the partially attenuated Rift Valley fever and Wesselsbron vaccine viruses. Specimens that should be submitted for laboratory investigation include either intact aborted foetuses and neonatal animals with congenital abnormalities, or samples of brain, spleen, liver, kidney, lung, placenta and serum or blood. Acute and convalescent phase sera from cows that abort may also be useful. Tissue samples fixed in buffered formalin for histopathological examination are unlikely to yield diagnostic results for Palyam serogroup viruses, but may be useful for eliminating alternative diagnoses.

Virus can be isolated from foetal tissues in cell cultures or suckling mice and identified as a member of the Palyam serogroup in immunofluorescence or complement fixation tests. Definitive identification of existing or new serotypes depends on performing neutralization tests with reference antisera to the known serotypes. However, the frequency of isolation of viruses of the serogroup from foetuses is very low.

Demonstration of antibodies in foetal sera is likely to be successful more frequently than isolation of virus, but it would be advisable to screen sera with a group-specific test, such as indirect immunofluorescence, before performing neutralization tests that are monospecific for individual serotypes, in order to avoid missing antibody to possible new serotypes. The dams of aborted foetuses are likely to have antibodies by the time abortion occurs, but it has been shown that it is possible to demonstrate rising titres in paired sera taken at the time of abortion and two or more weeks later. Again, screening for antibody with a group-specific test would be advisable, and the development of a test for IgM antibody activity may facilitate making a diagnosis of recent infection on the basis of testing a single serum sample.

Isolation of virus from neonatal animals with congenital abnormalities is less likely than from aborted foetuses, but the chances of detecting antibodies in pre-colostral sera are correspondingly greater,^{16, 17} and it is less likely that rising titres or IgM antibody will be detected in the sera of the dams.

Various group-specific molecular detection assays have been described, i.e. a nested RT-PCR assay targeting segment 3,¹  RT-PCR of segments 5, 7 and 9^{34, 49} and a real-time RT-qPCR assay targeting segment 5.¹⁰  

An experimental, formalin-inactivated cell culture vaccine against Kasba virus was developed in Japan.¹⁸ A trivalent vaccine composed of inactivated Aino, Akabane and Chuzan viruses has been described for the control of teratogenic arboviruses.²⁴

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