Unequal Evolutionary Rates in the Human Immunodeficiency Virus Type 1 (HIV-1) Pandemic: the Evolutionary Rate of HIV-1 Slows Down When the Epidemic Rate Increases

Human immunodeficiency virus type 1 (HIV-1) genetic diversity, due to its high evolutionary rate, has long been identified as a main cause of problems in the development of an efficient HIV-1 vaccine. However, little is known about differences in evolutionary rate between different subtypes. In this study, we collected representative samples of the main epidemic subtypes and circulating recombinant forms (CRFs), namely, subsubtype A1, subtypes B, C, D, and G, and CRFs 01_AE and 02_AG. We analyzed separate data sets for pol and env. We performed a Bayesian Markov chain Monte Carlo relaxed-clock phylogenetic analysis and applied a codon model to the resulting phylogenetic trees to estimate nonsynonymous (dN) and synonymous (dS) rates along each and every branch. We found important differences in the evolutionary rates of the different subtypes. These are due to differences not only in the dN rate but also in the dS rate, varying in roughly similar ways, indicating that these differences are caused by both different selective pressures (for dN rate) and the replication dynamics (for dS rate) (i.e., mutation rate or generation time) of the strains. CRF02_AG and subtype G had higher rates, while subtype D had lower dN and dS rates than the other subtypes. The dN/dS ratio estimates were also different, especially for the env gene, with subtype G showing the lowest dN/dS ratio of all subtypes.

Section: Discussionmentioning

confidence: 74%

Quantifying Differences in the Tempo of Human Immunodeficiency Virus Type 1 Subtype Evolution

Abecasis

Vandamme

Lemey

2009

“…The CRF01_AE epidemics among IDUs in both Stockholm and Helsinki involved slow as well as fast spread, which complicates dating because the molecular clock is inversely correlated to the rate of spread (23). However, for both the Swedish and Finnish data sets, the epidemic dynamics shown by the above ML analyses were also captured by Bayesian analyses, using a relaxed clock and two different growth models (the nonparametric skyline growth model and the logistic growth model).…”

Section: Resultsmentioning

confidence: 99%

“…Viruses which evolve at a measurable rate, like HIV, present unique opportunities to use molecular epidemiology to investigate the rate of spread, introduction dates, time between infections, and detailed phylodynamics (11,23,28,30). Thus, molecular epidemiology using HIV sequence data can provide information that is not readily accessible from pure epidemi-ological studies.…”

mentioning

confidence: 99%

Dynamics of Two Separate but Linked HIV-1 CRF01_AE Outbreaks among Injection Drug Users in Stockholm, Sweden, and Helsinki, Finland

Skar

Axelsson

Berggren

et al. 2011

Self Cite

The number of new CRF01_AE cases over a rooted phylogenetic tree accurately reflected the transmission dynamics and showed a temporary increase, by a factor of 12, in HIV incidence during the outbreak. Virus levels were similar in CRF01_AE and subtype B infections, arguing against differences in contagiousness. Similarly, there were no major differences in other baseline characteristics. Instead, the outbreak in Stockholm (and Helsinki) was best explained by an introduction of HIV into a standing network of previously uninfected IDUs. The combination of phylogenetics and epidemiological data creates a powerful tool for investigating outbreaks of HIV and other infectious diseases that could improve surveillance and prevention.

“…On the other hand, the virus must adapt to the local environment within a host during the course of infection, even at the cost of lowered transmissibility (12). Selection pressures during transmission/colonization and the course of infection can differ markedly, particularly for chronically infecting viruses (5,(12)(13)(14)(15). Some viral strains might excel at transmission and colonization because of their high replicative ability (colonizers), whereas other strains excel at escaping host immune selection (adaptors).…”

mentioning

confidence: 99%

New Insights into the Evolutionary Rate of Hepatitis B Virus at Different Biological Scales

Lin

Liu

Chien

et al. 2015

The evolutionary rates of hepatitis B virus (HBV) estimated using contemporary sequences are 10 2 to 10 4 times higher than those derived from archaeological and genetic evidence. This discrepancy makes the origin of HBV and the time scale of its spread, both of which are critical for studying the burden of HBV pathogenicity, largely unresolved. To evaluate whether the dual demands (i.e., adaptation within hosts and colonization between hosts) of the viral life cycle affect this conundrum, the HBV quasispecies dynamics within and among hosts from a family consisting of a grandmother, her 5 children, and her 2 granddaughters, all of whom presumably acquired chronic HBV through mother-to-infant transmission, were examined by PCR cloning and next-generation sequencing methods. We found that the evolutionary rate of HBV between hosts was considerably lower than that within hosts. Moreover, the between-host substitution rates of HBV decreased as transmission numbers between individuals increased. Both observations were due primarily to changes at nonsynonymous rather than synonymous sites. There were significantly more multiple substitutions than expected for random mutation processes, and 97% of substitutions were changed from common to rare amino acid residues in the database. Continual switching between colonization and adaptation resulted in a rapid accumulation of mutations at a limited number of positions, which quickly became saturated, whereas substitutions at the remaining regions occurred at a much lower rate. Our study may help to explain the time-dependent HBV substitution rates reported in the literature and provide new insights into the origin of the virus. IMPORTANCEIt is known that the estimated hepatitis B virus (HBV) substitution rate is time dependent, but the reason behind this observation is still elusive. We hypothesize that owing to the small genome size of HBV, transmission between hosts and adaptation within hosts must exhibit high levels of fitness trade-offs for the virus. By studying the HBV quasispecies dynamics for a chain of sequentially infected transmissions within a family, we found the HBV substitution rate between patients to be negatively correlated with the number of transmissions. Continual switching between hosts resulted in a rapid accumulation of mutations at a limited number of genomic sites, which quickly became saturated in the short term. Nevertheless, substitutions at the remaining regions occurred at a much lower rate. Therefore, the HBV substitution rate decreased as the divergence time increased. H epatitis B virus (HBV) is one of the most common infectious agents in the world. According to the World Health Organization (WHO), more than a third of the world's population (2 billion people) has been infected with HBV, and 240 million people among them are chronic carriers (1). Despite its importance, the evolutionary origins of HBV and the time scale of its spread remain elusive. For example, if the evolutionary history of HBV is calibrated using phylodynamic ph...