Evidence for possible biological advantages of the newly emerging HIV-1 circulating recombinant form from Malaysia - CRF33_01B in comparison to its progenitors - CRF01_AE and subtype B.
In Malaysia, co-circulation of CRF01_AE and subtype B has resulted in the emergence of the second generation derivative; CRF33_01B in approximately 20% of its HIV-1 infected individuals. Our objective was to identify possible biological advantages that CRF33_01B possesses over its progenitors. Biological and molecular comparisons of CRF33_01B against its parental subtypes clearly show that CRF33_01B replicated better in activated whole peripheral blood mononuclear cells (PBMCs) and CD4+ T-lymphocytes, but not monocyte-derived macrophages (MDMs). Also, its acquired fitness was greater than CRF01_AE but not subtype B. Moreover, CRF33_01B has higher rate of apoptotic cell death and syncytia induction compared to subtype B. These adaptive and survival abilities could have been acquired by CRF33_01B due to the incorporation of subtype B fragments into the gag-RT region of its full-length genome. Our studies confirm the previously held belief that HIV-1 strains may harbor enhanced biological fitness upon recombination. We therefore estimate a possible gradual replacement of the current predominance of CRF01_AE, as well as wider dissemination of CRF33_01B, together with the identification of other new CRF01_AE/B inter-subtype recombinants in Malaysia.
Lau
Katherine A
KA
Retroviral Genetics Division, Westmead Millennium Institute, Westmead Hospital, The University of Sydney, Westmead, NSW 2145, Sydney, Australia.
Wang
Bin
B
Miranda-Saksena
Monica
M
Boadle
Ross
R
Kamarulzaman
Adeeba
A
Ng
Kee-Peng
KP
Saksena
Nitin K
NK
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002478:Cells, Cultured; D005838:Genotype; D015726:Giant Cells; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000821:virology; D008296:Malaysia / Q000453:epidemiology; D011995:Recombination, Genetic; D014779:Virus Replication