also extremely adept at taking up DNA from their environment by natural transformation and incorporating it into their genomes, further contributing to their extraordinary variability. The end result of this considerable variation is a plethora of different surface compositions with which to bewilder the host adaptive immune system. It is therefore not surprising that it has been difficult to develop an effective vaccine against Neisseria infections, although there are now several that protect against Neisseria meningitidis, a common cause of fatal meningitis.
In contrast to the DNA rearrangements in bacteria and parasites, viruses rely on an error-prone replication mechanism for antigenic variation. Retroviral genomes, for example, acquire on average one point mutation every replication cycle, because the viral reverse transcriptase (see Figure 5–62) needed to produce DNA from the viral RNA genome lacks the proofreading activity of DNA polymerases. A typical, untreated HIV infection may eventually produce HIV genomes with every possible point mutation. By a process of mutation and selection within each host, most viruses change over time—from a form that is most efficient at infecting macrophages to one more efficient at infecting T cells, as described earlier (see Figure 23–17). Similarly, once a patient is treated with an antiviral drug, the viral genome can quickly mutate and be selected for its resistance to the drug. Remarkably, only about one-third of the nucleotide positions in the coding sequence of the viral genome are invariant, and nucleotide sequences in some parts of the genome, such as the Env gene (see Figure 7–62), can differ by as much as 30% from one HIV isolate to another. This extraordinary genomic plasticity greatly complicates attempts to develop vaccines against HIV. It has also led to the rapid emergence of new HIV strains. Nucleotide sequence comparisons between various strains of HIV and the very similar simian immunodeficiency virus (SIV) isolated from a variety of monkey species suggest that the most virulent type of HIV, HIV-1, may have jumped from primates to humans multiple independent times, starting as long ago as 1908 (Figure 23–31).
Influenza viruses are an important exception to the rule that error-prone replication dominates viral evolution. They are unusual in that their genome consists of several (usually eight) strands of RNA. When two strains of influenza infect the same host, the RNA strands of the two strains can reassort to form a new type of influenza virus. In normal years, influenza is a mild disease in healthy adults, although it can be life-threatening in the very young and very old. Different influenza strains infect fowl such as ducks and chickens, but only a subset of these strains can infect humans, and transmission from fowl to humans is rare. In 1918, however, a particularly virulent variant of avian influenza crossed the species barrier to infect humans, triggering the catastrophic pandemic of 1918 called the Spanish flu, which killed 20–50 million people worldwide. Subsequent influenza pandemics have been triggered by genome reassortment, in which a new RNA segment from an avian form of the virus replaced one or more of the viral RNA segments from the human form (Figure 23–32). In 2009, a new H1N1 swine virus emerged that derived genes from pig, avian, and human influenza viruses. Such recombination events allowed the new virus to replicate rapidly and spread through an immunologically naive human population. Generally, within two or three years, the human population develops immunity to a new recombinant strain of virus, and the infection rate drops to a steady-state level. Because the recombination events are unpredictable, it is not possible to know when the next influenza pandemic will occur or how severe it might be.