Molecular genetics of HIV-1 strains spreading in Russia Edward Karamov Ivanovsky Institute of Virology, Moscow 4th World Congress on Virology, 6-8 October 2014, San Antonio

Worldwide: 35 mln HIV+, 35 mln died In 2014: 2 mln new infections 1.3 mln deaths 14 mln receive HAART

Emergence of zoonoses:

Adapted from Ho & Bieniasz Cell, 2008 ABOBEC3G & TRIM5  are important for the host tropismus of HIV & SIV Restriction factors usually have broad antiviral activity HIV & SIV are resistant against the antiviral factors of their own hosts Adaptation of SIVcpz to chimpanzees paved the way for the spread of HIV-1 in humans: SIVcpz is resistant against human ABOBEC3G & TRIM5 

Specific features of HIV epidemic at this stage 1.The principal route of HIV transmission is still associated with intravenous drug use (60% in 2013) 2.Persons aged account for more than 60% of the HIV-infected population 3.A steady growth in the occurrence of HIV infection among women tends to persist 4.Intravenous drug use becomes more widespread, sex industry undergoes further development 5.The number of late-stage patients in need of antiretroviral chemotherapy increases

C 16% 6% D G 23% F (E,H) 5% A/B 0% А 8% В 42% А 86% В 5% C,D,G,F,H 4% A/B 5% HIV-1 subtypes in RUSSIA in 1994in 2000 Source: E.Karamov et al., 2000

Genetic subtypes of HIV-1 in Russia A/B (4%) A (93%) B (2%) Homogeneity (А - > 93%) (IDUs + heterosexuals) Low degree of genetic variability (2-8%)

Whole genome sequence of the CRF-02 A/G recombinant isolated from a patient with acute HIV-1 infection

UZBEKISTAN Phylogenetic tree of CFR02_AG recombinants 94 full-genome sequences: 12 countries + the first full-genome sequence from Russia OUTGROUP New A1 Sequence, Moscow New AG Sequence, Moscow SOUTH KOREA FRANCE Non-clustered: CAMEROON GHANA NIGERIA SENEGAL SPAIN CYPRUS USA

Full-length genome sequences obtained for ten Russian HIV isolates

Mosaic structure of the CRF63_02AG recombinant N. Shcherbakova et. al., AIDS Research and Human Retroviruses, 2014

Biological properties of HIV isolates Viral strainCellTCID 50 HIV-1 SK-8 PBMC 1.4∙10 3 HIV-1 IIIB СEM-SS 3.0∙10 5 HIV-1 Bru CEM-SS 1.6∙10 5 HIV-1 Uganda 455 MT4 2.5∙10 4 HIV-1 RiB-A\08 MT4 2.0∙10 4 Table 1. Comparison of infectious activity of HIV-1 PBMCCEM-SSMT4U937 HIV-1 SK HIV-1 IIIB ++++ HIV-1 Bru ++++ HIV-1 Uganda HIV-1 RiB-A/ Table 2. Replication ability of HIV-1 in PBMC and diverse cell lines CellsHIV-1 RiB-A/07 HIV-1 SK-8 Control (no virus) U 373 CD4CXCR U 373 CD4CCR Table 3. Tropism of Russian HIV-1 isolates to coreceptors HIV-1 strainSyncytium-inducing activityPhenotype HIV-1 SK-8 +/-NSI HIV-1 RiB-A/07 +/-NSI HIV-1 Uganda SI HIV-1 Bru +++SI HIV-1 IIIB ++++SI Table 4. Syncytium formation induced by HIV-1 strains HIV-1 strainAZT concentration, µМ HIV-1 SK HIV-1 RiB-A/ HIV-1 IIIB HIV-1 Bru Table 5. Levels of HIV-1 infection in the presence of diverse concentrations of AZT (percentages of inhibitor-free control)

Isolation of new HIV-1 strains Viruses isolated from early seroconverters or patients with acute HIV-1 infection; Most strains have the S/L phenotype; 70% strains fail to infect PBMC, 7% strains are dual tropic and phenotypically intermediate (between S/L- and R/H-forms).

Phenotypic properties of transmitted founder HIV-1 (new mosaic viruses A1  CRF63_02AG) More infectious; More Env per particle; Increased interaction with DC; More resistant to interferon alpha.

20. We [the G8 leaders)] remain committed to our Sea Island Summit initiative on creation of a Global HIV Vaccine Enterprise, and reaffirm our determination to bring it to fruition. We are convinced that there is a need to enhance the scientific and technical capacities in this area at the global, regional and national levels. In this regard, we welcome the Russian proposal to establish a regional coordination mechanism to promote HIV vaccine development in the countries of Eastern Europe and Central Asia, and call for this initiative to be carefully coordinated with the Global HIV Vaccine Enterprise. We also welcome coordination of activities and the cooperation between the Global HIV Vaccine Enterprise and other global initiatives and North/South partnerships active in this field, such as the European and Developing countries Clinical Trials Partnership (EDCTP) on clinical trials in Africa. G8 declaration on the fight against infectious diseases St. Petersburg, July 16, 2006

Acknowledgments: Institute of Virology, Russia G. Kornilaeva, F. Moskaleichik, A. Tatarintsev, A. Turgiev Institute of Immunology, Russia R. Khaitov, M. Khaitov, I. Sidorovich Instituto de Salud Carlos III, Spain M. Thomson National Cancer Institute, U.S.A. B. O’Keefe