Interference Among Group a Arboviruses

Abstract

Interference among group A arboviruses is described which does not involve the mediation of interferon. Interference was observed only if the interfering virus had an advantage over the challenge virus, either in time or in multiplicity of infection. Adsorption, penetration, and uncoating of challenge virus did not appear to be inhibited, but the synthesis of infectious viral ribonucleic acid of the challenge virus was significantly retarded. It was shown with temperature-sensitive viruses or mutants that the replication of viral ribonucleic acid by the interfering virus was required to establish interference. A mechanism of interference based on a competition for replication sites or substrates is compared with other possible explanations.The practical and theoretical implications of viral interference have stimulated considerable interest in this research area. Many reports have been published since the discovery of interference in plant viruses (14) and in animal viruses (11). Those papers that appeared prior to the discovery of interferon (13) have been reviewed extensively by Henle (10) and Schlesinger (18). The role of interferon as an important factor in the development of nonspecific resistance of the host cells to superinfection with a second related or unrelated virus is now firmly established (6). It is presently difficult to determine which of the early reports on viral interference were concerned with interferon production by the host or by other factors. It is apparent, however, that there are several types of viral interference that do not involve the mediation of interferon (5,7,12,(15)(16)(17) Cell cultures. Cell cultures were prepared from 10-day-old chick embryos. The chick embryo (CE) monolayers were grown, in lactalbumin hydrolysate medium containing 10% calf serum, for 24 hr at 37 C before infection. Details of the preparation of monolayers, medium, and growth conditions were described in an earlier paper (22).Virus growth. Except where noted, CE cell monolayers in 60-mm plastic petri dishes were infected with a virus seed prepared as a 10% CE seed, or as undiluted tissue culture fluids obtained from infected CE monolayers. The virus was allowed to adsorb for 15 min at room temperature; the cells were washed twice with phosphate-buffered saline (PBS) at pH 7.4 to remove excess unattached virus, and were overlayered with 5 ml of lactalbumin hydrolysate medium containing 10% calf serum. The cultures were incubated at 37 C in a 5% C02-95% air incubator.When the interfering and challenge virus were simultaneously added to CE monolayers, the virus seeds were mixed before infection of the cells. When the challenge virus was added at some time after infection of the cells with the interfering virus, the culture medium was removed, the challenge virus was added, and, after a 15-min adsorption period at room temperature, the infected cells were washed twice with PBS and overlayered with the lactalbumin hydrolysate medium. The cultures were reincubated at 37 C and samples of the culture medium were ...

Transmission of West Nile Virus by Culex quinquefasciatus Say Infected with Culex Flavivirus Izabal

“…aegypti previously infected with DENV still resulted in transmission of YFV, although mosquitoes were less susceptible to secondary infection with YFV. Similar findings have been reported in cell culture, where homologous superinfections were inhibited but secondary infection with a heterologous virus was permitted [22]–[25]. Therefore, based on previous observations, a primary infection of mosquitoes with a mosquito-specific flavivirus has the potential to interfere with infection or transmission of WNV acquired secondarily.…”

“…C6/36 cells persistently infected with Aedes aegypti densonucleosis virus remained permissive to infection with Haemagogus equinus densovirus (HeDNV), arguing against the induction of an anti-viral or immune state in the cells that would otherwise inhibit superinfection by this a similar virus [32]. However, interference between superinfecting alphaviruses in mosquito cell culture has been documented multiple times [22]–[24]. The cellular and molecular mechanisms that support replication of WNV in CxFV (+) cells are not known and require further study.…”

“…Thirdly, CxFV replication in mosquito cells is presumably similar to that of other flaviviruses due to similar genome organization [10], [13]. Zebovitz and Brown [22] determined that interference of superinfecting alphaviruses in cell culture was due to competition for replication sites or metabolites, and that viral RNA synthesis was necessary for inhibition of alphavirus superinfection. The non-structural proteins encoded by flaviviruses play important roles in virus replication and maturation [42], and the 5′ and 3′ untranslated regions contain conserved nucleotide sequences and RNA secondary structures involved in virus replication and translation [43].…”

Eilat virus induces both homologous and heterologous interference

“…Similarly, superinfection of A. albopictus cells persistently infected with CHIKV or SINV reduces virus titers of superinfecting heterologous viruses (UNAV, SFV, SINV, CHIKV, AURAV, and RRV) by ~10- to 1,000-fold (Eaton, 1979; Krapf et al , 1997). In addition, studies with chicken embryo cells infected with West Nile, yellow fever or VEEV viruses demonstrated ~25- to 10,000-fold reduction in superinfecting VEEV or EEEV titers (Lennette and Koprowski, 1946; Zebovitz and Brown, 1968). …”

“…Following its discovery, superinfection exclusion was also demonstrated with animal and mosquito-only viruses including alphaviruses (Bolling et al , 2012; Bratt and Rubin, 1968a; Claus et al , 2007; Geib et al , 2003; Hobson-Peters et al , 2014; Kenney et al , 2014; Kent et al , 2010; Laskus et al , 2001; Lee et al , 2005; Steck and Rubin, 1966a; Tscherne et al , 2007; Walters et al , 2004; Whitaker-Dowling et al , 1983; Zou, et al , 2009). The available in vitro data demonstrate that a prior alphavirus infection can reduce replication of a superinfecting homologous or heterologous virus (Adams and Brown, 1985; Eaton, 1979; Karpf et al , 1997; Lennette and Koprowski, 1946; Renz and Brown, 1976; Stollar and Shank, 1973; Zebovitz and Brown, 1968). These studies raise the intriguing possibility of utilizing alphaviruses as transmission control measures to limit or eliminate human and/or animal infection.…”