Abstract
In recent years, Hepatitis C virus 6a was not only the predominant subtype in Guangdong but also has the potential of increasing in non-Guangdong in China over time. To understand the virus evolution and transmission mode, the representative HCV 6a specimens in Guangdong province were chosen for deep sequencing and performed evolutionary analysis with all the 6a whole genome reference sequences. Our results showed that less than 5% of the genome was found to be under positive selection. The protein with the highest proportion of sites under positive selection was E1 and E2; A positive association between positive selection sites and the presence of CD8 epitopes was found in non-Guangdong genomes (χ2 = 9.168, P < 0.05). The evolutionary rate of 6a whole genome was 9.59×10− 4s/s/y. E2 has the fastest evolutionary rate (9.40×10− 3s/s/y), followed by E1, NS3 and NS5A. Spatio-temporal evolutionary analysis showed that Vietnam and other Southeast Asian countries were the origins of global HCV6a. Further, there were two important transmission modes which were all originated from Vietnam and other Southeast Asian countries in Guangdong. One (Group B) indicated that HCV6a was then transmitted to Hong Kong, and then to Guangdong and cross-dissemination between these two places; Another (Group C) revealed that HCV6a was directly disseminate to Guangdong and formed a regional epidemic. Our study firstly revealed the transmission mode of HCV6a by whole genome sequence, indicating that the impact of selective constraints in Guangdong and non-Guangdong, it can be helpful to plan for future prevention and management of HCV6a infection in Guangdong, China.