The impacts of HLA class I alleles on HIV-1 plasma virus The impacts of HLA class I alleles on HIV-1 plasma virus loads in a unique Asian population with a narrow spectrum of loads in a unique Asian population with a narrow spectrum of

HLA,and their changes at the population level over timeHLA,and their changes at the population level over time

Frequent Transmission of Cytotoxic-T-Lymphocyte Escape Mutants of Human

Immunodeficiency Virus Type 1 in the Highly HLA-A24-Positive Japanese Population

Tae Furutsuki, et al, JVI,2004

Adaptation of HIV-1 to human leukocyte antigen class I

Yuka Kawashima, et al, Nature,2009

0

10

20

30

400

10

20

30

400

10

20

30

40 (A) Japanese 29 alleles

(B) Caucasian (USA)

(C) African Americans (USA)

46 alleles

50 allelesAll

ele

freq

uen

cy

(%)

HLA-A; redHLA-B; yellowHLA-C; blue

24

51

57

5758

24

2

27

27

35

35

Alleles beneficial in U.S. are not protective in Japan

O’brien SJ, et al. Trends Mol. Med.2001

US Caucasians (n=600)

1 2 3 4 5 6 7

C*01B*13B*39B*46B*54B*55B*59B*35B*15A*26A*02B*52C*03C*04C*12A*31C*14B*40C*08C*06A*11B*51A*24C*07A*33B*67B*56B*44B*07C*15B*48

log10VL

Japanese (n=141)

Protective Allele frequencyB27;0.025%

B57;rare frequencyB51;8.6%

A11;10.4%Cw14:12.7%A26;11.6%

HLA-B51 has been losing its beneficial effect at the population level in Japan.

-2001 2002-2004 2005-1

2

3

4

5

6

(n=10) (n=9) (n=8)

B51+subjects

p=0.08p=0.48

HIV

-RN

A c

op

ies/

ml (

log

)

B51- B51+ B51- B51+1

2

3

4

5

6 p=0.048* p=0.420

(n=29) (n=10) (n=42) (n=8)

before 2001 after 2005

HIV

-RN

A c

op

ies/

ml

(lo

g)

-2001 2002-2004 2005-1

2

3

4

5

6

(n=20) (n=21) (n=33)

A24+subjects

p=0.38

p=0.63

HIV

-RN

A c

op

ies/

ml (

log

)

HLA-B51 has been losing its beneficial effect at the population level in Japan, however such transition was not obvious for the other alleles.