No abstract

To control plagues of free-living mice (Mus domesticus) in Australia, a recombinant murine cytomegalovirus (MCMV) expressing fertility proteins is being developed as an immunocontraceptive agent. Real-time quantitative PCR was used to monitor the transmission of two genetically variable field strains of MCMV through mouse populations after 25% of founding mice were infected with the N1 strain, followed by the G4 strain 6 weeks later. Pathogen-free wild-derived mice were released into outdoor enclosures located in northwestern Victoria (Australia). Of those mice not originally inoculated with virus, N1 DNA was detected in more than 80% of founder mice and a third of their offspring and similarly, G4 DNA was detected in 13% of founder mice and in 3% of their offspring. Thus, prior immunity to N1 did not prevent transmission of G4. This result is promising for successful transmission of an immunocontraceptive vaccine through Australian mouse populations where MCMV infection is endemic.

Feral house mice are a significant agricultural pest in south-eastern Australia. Fertility control is favoured as a long-term control strategy, using murine cytomegalovirus (MCMV) as a viral delivery system for an immunocontraceptive. We examined the impact of one and two non-sterilising field strains of MCMV on populations of house mice housed under semi-natural conditions. MCMV had no effect on the proportion of females pregnant or lactating or on the number of placental scars per female. However, females in enclosures with two strains of MCMV produced fewer litters. No impact of MCMV was detected on adult survival, with high survival (>95%) detected in all enclosures. Similar numbers of the first cohort of young entered the trappable population of all enclosures. There was no significant impact of MCMV on survival of young mice, although there was a trend for reduced numbers of the second cohort of young and less successful recruitment in enclosures with two strains of MCMV. The two cohorts of young mice in enclosures with MCMV had poorer body condition. These impacts of infection on young mice imply that MCMV may have negative effects on survival only when the host immune system is not fully developed or the host is immunocompromised. Overall, there was no effect of MCMV on the rate of increase of the mouse populations. Therefore, the effects of MCMV were minor at a demographic level, confirming the suitability of an Australian field strain of MCMV as a vector for an immunocontraceptive of mice.

Pest mammals have severe economic, environmental and social impacts throughout the world. Fertility control could reduce these impacts. Murine cytomegalovirus (MCMV) is being considered as an immunocontraceptive vector to control outbreaks of house mice (Mus domesticus) in Australian grain-growing regions. For successful control, a modified MCMV must transmit at a sufficient rate to keep populations of house mice below acceptable economic thresholds. We used disease models developed previously by using observations of free-ranging wild-mouse populations to assess the transmission rate of two laboratory strains of MCMV (N1 and G4) collected in a previous experiment. Mice contained in pens were deliberately infected with the N1 strain only, or with the N1 strain followed by the G4 strain. If we assume density-dependent transmission, which is the more likely mode of transmission, we found the N1 strain of MCMV transmitted at a rate~1/300 of the rate of field strains, and hence too slowly for successful virally vectored immunocontraception (VVIC). If transmission was frequency-dependent, the rate of transmission was~1/3 of the rate of field strains, and hence may allow successful VVIC. The G4 strain transmitted at least as slowly as the N1 strain, and possibly much more slowly; however, we could not determine whether this was an inherent property of the G4 strain or whether it was caused by competition with the N1 strain. Given the reliance of successful VVIC on rapid transmission, we recommend that future work in any VVIC system explicitly quantifies the transmission rate of recombinant viruses relative to field strains, both in the presence and absence of competing strains.