The First Cases of Hepatitis B Virus Subgenotype D4 Detection in Patients with Chronic, Acute, and Occult Hepatitis B in the Russian Federation

To study the molecular genetic structure of hepatitis B virus (HBV) D4 isolates first identified in the Russian Federation. Blood plasma samples of patients from the Republic of Dagestan with previously identified HBV subgenotype D4 were used in the work. For amplification and sequencing reaction, overlapping pairs of specific primers, jointly flanking the entire HBV genome, were used. HBV subgenotype D4 isolates were first detected in the Russian Federation. All 3 isolates were of the ayw2 serotype. Pharmacoresistance mutations L80V and M204I were found in the HIV-infected patient with HBsAg-negative occult HBV. A high frequency of natural polymorphic variants of the Pol gene was shown in all three isolates. In the Precore/Core region, Precore mutations A1846T, C1858T and Core mutations E40D, N74T, N87S, I97F were detected in all 3 isolates. In the X region, all 3 isolates had V5L and P38S mutations. Phylogenetic analysis of the full-length HBV genome showed that the isolates were grouped together with the subgenotype D4 isolate from South Africa. The origin of all three patients with the above isolates from the same geographic region, the phylogenetic proximity of the nucleotide sequences of the complete virus genomes, and a number of identical mutations and polymorphic variants in different genes in all three isolates indicate an independent single import of the virus with the subsequent spread. The routes of distribution, as well as the frequency of HBV D4 occurrence in the Republic of Dagestan, remain unknown and require further research.