Molecular genetics of HIV-1 Molecular genetics of HIV-1 strains spreading in Russia 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 diedIn 2014: 2 mln new infections
1.3 mln deaths 14 mln receive HAART
Emergence of zoonosesEmergence of zoonoses::
Adapted fromHo & 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 theantiviral 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 15-30 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/B0%
А
8%
В42%
А86%
В5%
C,D,G,F,H4% A/B
5%
HIV-1 subtypes in RUSSIAHIV-1 subtypes in RUSSIA
in 1994 in 2000Source: E.Karamov et al., 2000Source: E.Karamov et al., 2000
Genetic subtypes of HIVGenetic subtypes of HIV-1 -1 in Russiain Russia
A/B (4%)
A (93%)
B (2%)Homogeneity
(А - > 93%)(IDUs + heterosexuals)
Low degree ofgenetic 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 CFRPhylogenetic tree of CFR02_02_AG recombinantsAG recombinants
94 full-genome sequences: 12 countries + the first full-genome sequence from Russia
OUTGROUPNew A1 Sequence,Moscow
New AG Sequence,Moscow
SOUTHKOREA
FRANCE
Non-clustered:
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Full-length genome sequences obtained for Full-length genome sequences obtained for ten Russian HIV isolatesten Russian HIV isolates
Mosaic structure of the CRF63_02AG recombinantMosaic structure of the CRF63_02AG recombinant
N. Shcherbakova et. al., N. Shcherbakova et. al., AIDS Research and Human RetrovirusesAIDS Research and Human Retroviruses, 2014, 2014
Biological properties of HIV Biological properties of HIV isolatesisolates
Viral strain Cell TCID50
HIV-1SK-8 PBMC 1.4∙103
HIV-1IIIB СEM-SS 3.0∙105
HIV-1Bru CEM-SS 1.6∙105
HIV-1Uganda 455 MT4 2.5∙104
HIV-1RiB-A\08 MT4 2.0∙104
Table 1. Comparison of infectious activity of HIV-1Table 1. Comparison of infectious activity of HIV-1
PBMC CEM-SS MT4 U937HIV-1SK-8 + - + -HIV-1IIIB + + + +HIV-1Bru + + + +
HIV-1Uganda 455 - + + +HIV-1RiB-A/07 + + + +
Table 2. Replication ability of HIV-1 in PBMC and diverse cell linesTable 2. Replication ability of HIV-1 in PBMC and diverse cell lines
Cells HIV-1RiB-A/07 HIV-1SK-8 Control (no
virus)U373 CD4CXCR4 3.225 2.909 0.024
U373 CD4CCR5 3.203 2.497 0.010
Table 3. Tropism of Russian HIV-1 isolates to coreceptorsTable 3. Tropism of Russian HIV-1 isolates to coreceptors
HIV-1 strain Syncytium-inducing activity Phenotype HIV-1SK-8 +/- NSI
HIV-1RiB-A/07 +/- NSIHIV-1Uganda455 +++ SI
HIV-1Bru +++ SIHIV-1IIIB ++++ SI
Table 4. Syncytium formation induced by HIV-1 strainsTable 4. Syncytium formation induced by HIV-1 strains
HIV-1 strain
AZT concentration, µМ100 10 1 0.1 0.01 0.001
HIV-1SK-8 3 4 4 6 28 75HIV-1RiB-A/07 55 65 66 78 86 82
HIV-1IIIB 9 21 23 40 58 100HIV-1Bru 0 0 2.6 27.1 88.5 88.5
Table 5. Levels of HIV-1 infection in the presence of diverse concentrations of AZT (percentages of inhibitor-free control)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 strainsIsolation 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 Phenotypic properties of transmitted founder HIV-1 (new mosaic viruses A1 HIV-1 (new mosaic viruses A1 CRF63_02AG) 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 G8 declaration on the fight
against infectious diseases against infectious diseases St. PetersburgSt. Petersburg, , July July 1616, , 20062006
Acknowledgments:
Institute of Virology,RussiaG. Kornilaeva,F. Moskaleichik,A. Tatarintsev,A. Turgiev
Institute of Immunology,RussiaR. Khaitov, M. Khaitov,I. Sidorovich
Instituto de Salud Carlos III,SpainM. Thomson
National Cancer Institute,U.S.A.B. O’Keefe