The Evolutionary Dynamics of a Rapidly Mutating Virus within and between Hosts: The Case of Hepatitis C Virus

Many pathogens associated with chronic infections evolve so rapidly that strains found late in an infection have little in common with the initial strain. This raises questions at different levels of analysis because rapid within-host evolution affects the course of an infection, but it can also affect the possibility for natural selection to act at the between-host level. We present a nested approach that incorporates within-host evolutionary dynamics of a rapidly mutating virus (hepatitis C virus) targeted by a cellular cross-reactive immune response, into an epidemiological perspective. The viral trait we follow is the replication rate of the strain initiating the infection. We find that, even for rapidly evolving viruses, the replication rate of the initial strain has a strong effect on the fitness of an infection. Moreover, infections caused by slowly replicating viruses have the highest infection fitness (i.e., lead to more secondary infections), but strains with higher replication rates tend to dominate within a host in the long-term. We also study the effect of cross-reactive immunity and viral mutation rate on infection life history traits. For instance, because of the stochastic nature of our approach, we can identify factors affecting the outcome of the infection (acute or chronic infections). Finally, we show that anti-viral treatments modify the value of the optimal initial replication rate and that the timing of the treatment administration can have public health consequences due to within-host evolution. Our results support the idea that natural selection can act on the replication rate of rapidly evolving viruses at the between-host level. It also provides a mechanistic description of within-host constraints, such as cross-reactive immunity, and shows how these constraints affect the infection fitness. This model raises questions that can be tested experimentally and underlines the necessity to consider the evolution of quantitative traits to understand the outcome and the fitness of an infection

Actions of the respiratory muscles or how the chest wall moves in upright man

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Mechanical role of the abdominal muscles in relation to posture

Abdominal muscle activity was studied in 10 normal naive subjects during quiet breathing in different body positions. Electromyograms of the upper and lower portions of the external oblique and rectus abdominis were recorded with bipolar needle electrodes and changes in abdominal and rib cage displacements were measured using linearized magnetometers. The abdominal muscles were always silent in the supine posture. In contrast, 8 of the 10 subjects showed tonic abdominal muscle activity in the standing posture and 4 of the subjects did so also in the 45° head-down position; when present, this activity was always greater in the dependent (where the hydrostatic pressure was greater) than in the non-dependent portion of the muscles. Tonic abdominal muscle activity was associated with a reduction of abdominal volume throughout the respiratory cycle and a reduction of the end-expiratory lung volume below the neutral position of the respiratory system. We conclude that (1) tonic activity is present in the abdominal muscles in most standing subjects, (2) this activity is primarily related to the magnitude of hydraulic pressure exerted by the abdominal contents on the abdominal wall, and (3) in most normal individuals standing at rest, the end-expiratory position is at least in part actively determined. Such an abdominal muscle use, although causing quiet breathing to depart from the relaxed abdominothoracic configuration, may be associated with minimum respiratory work.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Les muscles respiratoires et la cage thoracique pendant la respiration calme.

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Mechanical action of the abdominal muscles

SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

Effect of hyperinflation on the diaphragm

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Relationship between neural drive and mechanical effect in the respiratory system

SCOPUS: cp.kinfo:eu-repo/semantics/publishe

Mechanics of the chest wall during restrictive thoracic strapping

SCOPUS: ar.jinfo:eu-repo/semantics/publishe