Replication of Virus and Human Transmission: H5N1 Virus
Viruses are the simplest of all life forms. They can be viewed as selfish genes with the single-minded purpose to replicate. Viruses are parasites, and their replication depends strictly on the machinery of cellular organisms. They have developed vehicles that allow for efficient transfer of their genes into host cells, supporting virus replication.
Replication of viruses is rarely subtle; instead it commonly results in damage or even death of the invaded cells. Hosts have in turn developed defense mechanisms against this invasion. Mechanisms used directly by the attacked cells to block virus entry or replication of viruses have evolved to protect individual cells and are employed by both primitive monocellular organisms such as bacteria and sophisticated mammalian hosts alike.
More complex organisms have also developed specific organs and cells to form an immune system to ward off invading pathogens. In turn, viruses, which are much more flexible than their hosts because of their rapid replication of viruses allowing for genetic modifications, are constantly mutating to dodge the defense mechanisms of their unwilling production facilities.
Altogether, >400 viruses cause disease in their human hosts. More than 100 of those belong to the Rhinovirus genus. Considering the multitude of viruses that are pathogenic in humans, it is not surprising that in spite of advances in modern medicine, viral infections remain one of the leading causes of human morbidity and mortality worldwide.
Constant evolution allows more efficient replication of viruses, in part through an increase in host range from animals to humans. Therefore, although not long ago governments of some developed countries declared infectious diseases a problem of the past, the fight against infectious diseases became one of the main topics of the last G-8 summit, the meeting of eight of the world’s leading industrialized nations.
One major current threat is a new influenza A virus pandemic of potentially catastrophic outcome. Three influenza A virus pandemics struck in the last century. The influenza pandemic of 1918 killed more young Americans than all of the wars of the twentieth century combined and claimed an estimated 20 to 50 million human lives globally. Additional pandemics occurred in 1957, which caused approximately 2 million human deaths, and in 1968, which resulted in approximately 1 million human deaths.
The currently evolving H5N1 virus, which could be the precursor for the next pandemic, has disturbing similarities to the highly virulent virus of 1918, which was reconstructed through reverse genetics with the help of bits and pieces of viral genome isolated from a human cadaver that had been preserved in the arctic permafrost. H5N1 virus was first detected in Asian poultry in 1997. By July 2006, 229 human cases of H5N1 virus infection had been reported, mainly from Asia, but also from Africa and Europe. These cases resulted in 131 fatalities, which is far in excess of previously observed mortality rates of influenza A virus infections. So far the virus has been transmitted by human contact with infected birds, and only a few isolated cases suggest direct human-to-human transmission. Further mutations of H5N1 virus, either in the form of adaptive point mutations, that is, antigenic drift, or through resentment in humans concomitantly infected with a different influenza A virus, called antigenic shift, could eventually allow for sustained and efficient human-to-human transmission.
The human immunodeficiency virus (HIV)-1 was first identified in 1981. It evolved from a simian immunodeficiency virus that infects chimpanzees and crossed the species barrier less than 100 years ago. Since then it has gained an irreversible foothold in the human population.
A corona virus that had spilled over for years into humans from a yet-to-be-identified animal reservoir failed to cause serious symptoms, but then suddenly began to result in life-threatening acute respiratory infections in 2003. This change in virulence was the result of a deletion mutation within the viral genome.
Vaccines are currently available for only a fraction of the identified human viral pathogens. Vaccines to viruses that only infect humans, that is, without an animal reservoir, can eradicate a virus, as was shown for smallpoxvirus, which was eliminated through global vaccination campaigns by 1977. Other human viruses for which vaccines are available, such as poliovirus, measles virus, or hepatitis B virus, could potentially be eliminated by global mass vaccination as well.