Tracing the evolutionary history of hepatitis B virus genotype H endemic to Mexico

Abstract

Hepatitis B virus (HBV) spreads efficiently among all human populations worldwide. HBV is classified into ten genotypes (A to J) with their geographic distribution and clinical features. In Mexico, HBV genotype H is the leading cause of hepatitis B and has been detected in indigenous populations, suggesting that HBV genotype H may be native to Mexico. However, little is known about the evolutionary history of HBV genotype H. Thus, we aimed to determine the age of HBV genotype H in Mexico using molecular dating techniques. Ninety-two HBV sequences of the reverse transcriptase (RT) domain of the polymerase gene (~1,251 bp) were analyzed; 48 were genotype H, 43 were genotype F, and the oldest HBV sequence from America was included as the root. All sequences were aligned, and the most recent common ancestor (TMRCA) time was calculated using the Bayesian Skyline Evolutionary Analysis. Our results estimate a TMRCA for the genotype H in Mexico of 2070.9 (667.5–4489.2) years before the present (YBP). We identified four major diversification events in genotype H, named H1, H2, H3, and H4. The TMRCA of H1 was 1213.0 (253.3–2638.3) YBP, followed by H2 1175.5 (557.5–2424.2) YBP, H3 949.6 (279.3–2105.0) YBP, and H4 1230.5 (336.3, 2756.7) YBP. We estimated that genotype H diverged from its sister genotype F around 8140.8 (1867.5–18012.8) YBP. In conclusion, this study found that genotype H in Mexico has an estimated age of 2070.9 (667.5–4489.2) YBP and has experienced at least four major diversification events since then.

Host and HBV Interactions and Their Potential Impact on Clinical Outcomes

“…HBV sub-genotypes are typically designated using a combination of letters and numbers (for example, A1, A2, B1, B2, etc.). The classification of HBV in genotypes and sub-genotypes has important clinical implications, including their association with disease progression, response to antiviral therapy, and global distribution [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. HBV genotypes A, B, C, and D were discovered simultaneously in 1988, and four years later, genotypes E and F were proposed [ 12 , 13 ].…”

“…Genotype G is mainly detected in the risk group of men who have sex with men (MSM) from Mexico, the United States, France, and the Netherlands [ 23 , 24 ]. Genotype H is endemic mainly to Mexico [ 25 ]. Genotypes I and J have also been reported in Southeast Asia [ 18 , 19 ].…”

“…This type of adaptation has been observed in the native population of Mexico infected with genotype H [ 106 ]. Molecular dating estimates that genotype H has been present in the Mexican population for at least 2070 years [ 25 ]. Another virus with a similar adaptation may be the sub-genotype F1b in the Amerindian population of the Amazon basin [ 107 ].…”

Hepatitis B Virus Genotype H: Epidemiological, Molecular, and Clinical Characteristics in Mexico

“…Interestingly, the finding of human skeleton remains while excavating beneath Mexico City's Ex-Hospital Real de San José de las Naturales led to the sequencing of HBV-DNA from a human tooth, revealing an HBV/H strain (SJN013) [1]. This ancestral virus sequence provided the reference to adjust the molecular clock for dating Mexican HBV sequences [128]. This remarkable anthropological and molecular discovery also broadens the hunt for the causes of the great Mesoamerican epidemics that occurred after the advent of the Spanish conquerors and whether they were responsible for the deaths of millions of natives.…”

“…It is also related to the establishment and transition to a sedentary lifestyle of these ethnic groups in Mesoamerica, which presently corresponds to the geographical region of what is now Mexico and part of Central America. Following the original dispersal, four clades (H1-H4) have emerged and may eventually evolve into subgenotypes [128].…”