Cross-Species Virus Transmission and the Emergence of New Epidemic Disease by Colin Parrish, et al addresses how strains of epizootic and enzootic viruses cause epidemics in human populations. Enzootic disease, such as simian immunodeficiency viruses (SIVs) and human immunodeficiency viruses (HIVs), are pathogens that regularly affects animals at a particular season or district. Epizootic diseases, such as virulent influenza strains, are the equivalent of an epidemic in animal populations in which a particular pathogen temporarily expresses a higher frequency of symptoms in an animal population. In order to understand how epidemics in humans occur, Parrish outlines the importance of understanding the pathogens' transfer process between the main animal reservoir and the human host, its compatibility with the new host, and viral fitness after transfer.
The physical barrier between animal reservoir and humans can be breached many ways, ecologically, agriculturally, and behaviorally. Animals that did not have previous contact with humans can be brought in to closer proximity through agriculture. The fruit bat, for example, is an epizootic host for Nipah virus, SARS CoV, and possibly Ebola virus. They are neutral carriers of the disease and they can pass it onto pigs, and other intermediate hosts, that can then bring the pathogen into closer contact with humans. In the wild it is geologically and behaviorally unfavorable for bats to come into close contact with intermediate hosts such as pigs; however when a large orchard of fruit trees is planted right next to a pig farm, two demographically and behaviorally separated niches are now brought into close contact through changes in agricultural. The viruses can be transmitted to humans through infected tissue of the pigs, or respiratory droplets of infected pigs. An example that illuminates the use of intermediate vectors and human behavior for viral transmission to humans is Simian Immunodeficiency Virus (SIV) in old world primates. Old world primates transferred the virus to chimpanzees, which then transferred it to humans. As population density and sexual promiscuity increased around the world, the virus has access to a huge host reservoir. Another example of how population density affects a virus's chance at survival in human hosts is the spread of influenza. Birds are regular carriers of influenza and their migratory patterns enable them to spread their pathogens all around the world. A common intermediate host for influenza is pigs, but avian strains have also been cultured from humans. The density of human populations and behavior of humans determines how fast the virus spreads. If the population density of an infected individual is low, the spread of the virus will not produce an epidemic. Even with favorable human behavior and high population densities, not all pathogen transfers are successful. Most of the transfers between old world primates and human hosts resulted in dead end transfers and many avian flu strains cultured from humans have not resulted in epidemics. Once a pathogen enters its new host, it must breach the molecular barriers that may preclude its transformation.
In order to establish virulence in its new host pathogens must breach host cell responses, have compatibility with the host tissue and receptor binding, and contain the right combination of viral replication proteins. Influenza has caused many deadly epidemics, however, many of the strains acquired from animal reservoirs have resulted in dead-end spillover events. Many avian flu infections in humans result in dead-end events because one of the surface proteins of influenza, neuraminidase, is inactivated by the glycans secreted by bacteria in mammalian intestinal tracts. The other surface receptor of avian influenza, hemagglutinin, does not recognize the sialic acids found on the surface of human cells and therefore has not been able to establish virulence in the population. If the pathogen does breach the surface and gain entry into the cell, interferon responses by the host may effectively restrict some pathogens after it enters the cell. If the pathogen does have compatibility with host tissue and surface cell receptors, it will still need the right combination of viral replication proteins in order to transform in the host. Many polyomaviruses regulate DNA replication by recognizing specific sequences around the origin. If the viral T antigens that recognize the origin of DNA replication are not specific for that DNA origin then replication cannot take place.
The accumulated mutations that allow a pathogen entry and replication in its new host often decrease its rate and progress of adaption. Although poorly understood, evidence suggests complex epistatic interactions between virus and host may play a role in compensating for deleterious mutations that would limit viral fitness. The study of retroviruses such as vesticular stomatis virus, HIV-1, and bacteriophage j6 have provided information on how deleterious mutations are compensated for by epistatic interaction, compensatory mutations at different loci, and reversion to wild type state. The ability of a virus to overcome low fitness viability may also be impacted by the frequency of viral transfers from human-to-human. If the virus is transferred often, it has an increased chance at fitness recovery then an isolated virus in a dead-end host. In a new host the virus may have more compatibility and lower competition. In SARS CoV, for example, lower viral transmission decreased viral fitness in some hosts but in other hosts it had a high rate of transmission, affording it the chance to maintain viral fitness.
Steps are being taken at each point in the transfer of a virus from its reservoir to new host to minimize the impact of new diseases. Migratory patterns of birds, and people, are documented and analyzed to quell the next outbreak before it reaches epidemic proportions. Large populations of livestock reservoirs are carefully monitored for possible outbreaks, vaccinated and culled as part of a global effort to thwart viral transmission. Research advances are increasing our understanding of how virus's breach host molecular barriers and how viruses achieve fitness after successful entry. Broad areas of research may shed light on new preemptive strategies for endemic control of cross-species virus transmission. In my opinion, researchers should focus their efforts on maintaining sanitary conditions in livestock and on how human behavior facilitates viral spreading. Many deadly viral impacts come from dense population of livestock that act as intermediates to human hosts and human behavior has facilitated the spread of many these viruses. It is impossible to know when and where the next virus will attack, and medications seem to always be one step behind, but education about how human behavior facilitates the spread of viruses would be a productive area of research.
