A Comparison of the Biological Characteristics of EV71 C4 Subtypes from Different Epidemic Strains

The comparative analysis of the biological characterization and the genetic background study of EV71 circulating strains is commonly recognized as basic work necessary for development of an effective EV71 vaccine. In this study, we sequenced five EV71 circulating strains, isolated from Fuyang, Hefei, Kunming and Shenzhen city of China and named them FY-23, FY-22, H44, K9 and S1 respectively. The sequence alignment demonstrated their genotypes be C4. The genetic distance of the VP1 gene from these isolates suggested that they were highly co-related with genetic identity similar to other previously reported EV71 strains in China. Additionally, these strains were identified to display some obvious proliferation dynamics and plaque morphology when propagated in Vero cells. However, a distinctive difference in pathogenic ability in neonatal mice was found. Some differences in cross neutralization test & immunogenic analysis were also found. All these results are related to the biological characterization of circulating EV71 strains in China and aid in the development of an EV71 vaccine in the future.

Global Transmission of Human Immunodeficiency Virus 1 Subtype C and Its Impact on the Circulation of B/C Recombination Strains in China

This study aimed to reconstruct the origin and worldwide epidemic history of human immunodeficiency virus(HIV)1 subtype C and comprehend how HIV-1 subtype C was introduced into and spread throughout China in the formof B/C recombinant strains.Envelope sequences ofHIV-1 subtype C and some other subtypes deposited before December 31,2020 were downloaded from the Los Alamos HIV Database and the Chinese National Center for AIDS/STD Control and Prevention Database.The available sequences were screened for quality,and Bayesian analysis was used to build the maximum clade credibility evolutionary tree to analyze and judge the origin and spread of HIV-1 subtype C.HIV-1 subtype C originated in central Africa around 1952,then spread to southern Africa around 1969 and to eastern Africa around 1973.HIV-1 subtype C fromsouthern Africa was introduced into India in 1977.HIV-1 subtype C of eastern Africa was introduced into Brazil in 1987.Indian HIV-1 subtype C was exported to China in three migration events during the period from 1986 to 1989.The two predominant recombinants in China(CRF07_BC and CRF08_BC)emerged in 1988 and 1990,respectively.Other B/C recombinants,namely,CRF64_BC,CRF61_BC and CRF62_BC,originated in 1993,2002 and 2000,respectively.Our study has reconstructed the global origin and evolutionary history of HIV-1 subtype C.In addition,our study demonstrated that the Chinese HIV-1 subtype C originated from three related Indian lineages around the mid to late 1980s and,since then,has formed some B/C recombinants with subtype B that caused a widespread epidemic in China.

Use of Mutual Information Arrays to Predict Coevolving Sites in the Full Length HIV gp120 Protein for Subtypes B and C

It is well established that different sites within a protein evolve at different rates according to their role within the protein; identification of these correlated mutations can aid in tasks such as ab initio protein structure, structure function analysis or sequence alignment. Mutual Information is a standard measure for coevolution between two sites but its application is limited by signal to noise ratio. In this work we report a preliminary study to investigate whether larger sequence sets could circumvent this problem by calculating mutual information arrays for two sets of drug naive sequences from the HIV gpl20 protein for the B and C subtypes. Our results suggest that while the larger sequences sets can improve the signal to noise ratio, the gain is offset by the high mutation rate of the HIV virus which makes it more difficult to achieve consistent alignments. Nevertheless, we were able to predict a number of coevolving sites that were supported by previous experimental studies as well as a region close to the C terminal of the protein that was highly variable in the C subtype but highly conserved in the B subtype.

Stability of HIV-1 subtype B and C Tat is associated with variation in the carboxyl-terminal region

The multifunctional trans-activator Tat is an essential regulatory protein for HIV-1 replication and is characterized by high sequence diversity. Numerous experimental studies have examined Tat in HIV-1 subtype B, but research on subtype C Tat is lacking, despite the high prevalence of infections caused by subtype C worldwide. We hypothesized that amino acid differences contribute to functional differences among Tat proteins. In the present study, we found that subtype B NL4-3Tat and subtype C isolate HIV1084 i Tat exhibited differences in stability by overexpressing the fusion protein Tat-Flag. In addition, 1084 i Tat can activate LTR and NF-κB more efficiently than NL4-3 Tat. In analyses of the activities of the truncated forms of Tat, we found that the carboxylterminal region of Tat regulates its stability and transactivity. According to our results, we speculated that the differences in stability between B-Tat and C-Tat result in differences in transactivation ability.