Influenza A virus is the most pathogenic of the human influenza viruses. Its envelope encloses a protein complex (vRNP) and eight, single-stranded, negative RNA (the complement of a positive RNA strand that can be transcribed by a ribosome) segments (vRNA). Each segment encodes one or two proteins that support viral replication. On the outer surface of the envelope are proteins that recognize and bind to host receptors.

A. Annotate the representation below to briefly describe each process associated with a numbered label.

Figure 21.27

B. Describe influenza A viral replication as a process regulated by either positive or negative feedback and justify your selection.

C. The human-acquired immunodeficiency syndrome (AIDS) and many cancers are cause by double-stranded RNA retroviruses.

Contrast the processes of viral replication of HIV and influenza A virus.

D. Explain the difference in the effects of infection by HIV and influenza A virus on host genetic variability.

E. Measured mutation rates for influenza A virus and HIV are nearly identical (Sanjuan et al., Jour. Virology, 2010). Explain this observation even though host error-checking operates in one of these replication modes.

A. Three-dimensional (3D) structures, or folding, of proteins have been shown to contain more information about evolutionary relationships than the sequences of DNA nucleotides that encode the proteins. Amino acid sequences of rabbit skeletal muscle actin (375 amino acids) and bovine ATPase (386 amino acids) have only 39 locations in common. However, the 3D structure of these proteins are nearly identical (Flaherty et al., Proc. Natl. Acad. Sci. USA, 1991). As information about the 3D folding of proteins and the number of sequenced whole genomes has increased, folding has been shown to be an evolutionarily conserved property.

Analyze these data to refine the following model: The evolutionary history of life on Earth can be inferred from variations over time of the nucleotide sequence of a gene.

B. By applying a classification scheme based on protein folding, Nasir and Caetano-Anollés (Sci. Adv. 2015) have determined the number of folding families that viruses share with the three domains. Approximately 60% of the folding patterns found in viruses were common to all three domains, as shown below. Fewer than 10% were unique to viruses.

Figure 21.28

Viruses are acellular, and, consequently, they lie outside of the three domains of cellular life. However, their exclusion is increasingly challenged. Since 2012, several very large viruses have been discovered, each a double-stranded DNA virus with more than one million bases, with some encoding nucleotides and amino acids. However, none encode ribosomes, so these viruses are still dependent on a marine bacteriovore (amoeba or flagellate) host for replication.

Hypotheses regarding the origin of life on Earth need to account for the relationship between proteins and genetic information. Proteins are required to read and write genetic information, but genetic information is required to synthesize proteins. Which of these systems evolved first, and if neither came first, how could they evolve simultaneously? The RNA-first model is based on the idea that ribosomal RNA both encodes and synthesizes proteins.

Describe a hypothesis for the origin of life on Earth that combines the dual functionality of RNA and the function of retroviral reverse transcriptase to propose a mechanism leading to an ancient, acellular lineage of very large, double-stranded DNA viruses and a first DNA-based cellular life form.

C. Like viruses, the nucleus of a eukaryote uses the machinery of the cell to transcribe DNA and synthesize proteins. Evaluate the possibility of the origin of Eukarya by specialization of a very large double-stranded DNA virus.

Viruses evolve but leave no fossil evidence that can be used to construct phylogenies. However, viral DNA, especially that of retroviruses, is commonly found in the host genome. By comparing sequences from the same virus integrated at different points in time, the evolutionary history of the virus can be constructed. The viral genomes are typically found incomplete, in segments, and interrupted by stop codons. In jawed vertebrates, retroviral sequences or sequences that have been derived from them are a significant fraction of the whole genome.

A. Explain why retroviral DNA rather than the genomes of single-stranded or double-stranded DNA or single-stranded RNA viruses are found in host DNA.

B. Exaptation occurs when gene expression provides a function that is independent of the selection pressures that have acted on the gene. For example, a pigment that provided selective advantage by reducing damage from solar radiation becomes an element of mating behavior. Feathers that evolved under selection to prevent heat loss become a means of flight.

In a study of viral evolution within host genomes of primates, Katzuorakis and Gifford (PLOS Genetics, 2010) found that viral genomes within the host were surprisingly stable; with computer simulation, they estimated the probability of such constancy at 1 in 100,000.

Explain in terms of selection how viral genetic information that no longer replicates the virus is maintained by the host.

C. Distemper is an incurable disease of cats, dogs, and their sister lineages caused by a parvovirus. The virus exploits the host’s transferrin, a membrane-bound protein used for iron transport, to attach to the cell. The phylogeny of the Parvoviridae family has been constructed (J. Kaebler, PLOS Pathogens, 2012). That study revealed the evolution of both the virus and the host protein through selection to resist infection. About 54 million years ago when the lineage of cats (Feliformia) diverged from that of dogs (Caniformia), the parvovirus envelope diverged as well, conforming to changes in the host’s transferrin. In 1978, a worldwide disease in dogs due to a parvovirus suddenly appeared.

Explain how this pandemic could have originated in the cat population.

A. A simple calculation of the rate of spread of a pox virus (virion) led researchers at Imperial College London to a new insight. Virions communicate with other virions. The researchers observed that the radius of an approximately circular plaque of infected cells grew to 1.45 mm in just 3 days. They measured the distance between adjacent cells to be 0.037 mm to obtain the apparent time for the lytic cycle (from infection to lysis). They compared this time to the actual rate at which new virions are formed: 5 to 6 hours.

A. Predict the radius of infection if the infection process involved a sequence of entry, replication, lysis, and infection of an adjacent cell.

To account for this discrepancy between observed and predicted growth rates, the researchers examined the viral entry process and discovered that the actin protein on the host cell’s surface that provided the viral receptor was modified by attachment. They then found a mutant virus that did not modify the cell surface protein. The dependence of the growth of plaque radius on time for the wild type and mutant are shown in the graph.

Figure 21.29

B. Analyze these data and compare the infection rates calculated with those predicted in part A.

C. Use the results of this experiment to support the claim that responses to information and communication of information affect natural selection.

Describe how viral replication introduces genetic variation in the viral population.