AEGiS-14IAC: Ex vivo fitness studies provides evidence for the natural attenuation of human immunodeficiency virus type 1 subtype C during the AIDS epidemic.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Ex vivo fitness studies provides evidence for the natural attenuation of human immunodeficiency virus type 1 subtype C during the AIDS epidemic.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrA1384)

Arts EJ, Ball SC, Abraha A
Case Western Reserve University, Cleveland, United States

BACKGROUND: HIV-1 evolves and migrates through individual hosts, overcoming barriers to transmission and avoiding immune responses. How will this continual evolution and expansion within the human population affect HIV-1 virulence? We have recently shown that ex vivo HIV-1 fitness (or competitive replication efficiency) is a strong correlate of intrapatient disease progression (Quniones et al., 2000, J. Virol. 74:9222). Current studies suggest a relationship between fitness, progression, and subtype prevalence. Attenuated replication of subtype C may result in slow progression to AIDS, increased time for transmission, and increased prevalence in the epidemic.

METHODS: Six subtype C and nine B HIV-1 isolates were used to infect PBMC and other primary human cells in pairwise competition experiments. A heteroduplex tracking technique was then used to measure the relative production in a dual HIV-1 infection.

RESULTS: All subtype C HIV-1 isolates were less fit than subtype B isolates (p < 0.0001). However, intrasubtype variations in fitness were not significant. Subtype C isolates also appear less fit than subtype A and D isolates. Increased replication of subtype B over subtype C HIV-1 isolates was also observed in primary macrophages and CD4+ T cells. However, subtype C isolates were more fit in skin-derived Langerhan cells (LC). Ultimately, efficiency of host cell entry predicted the winner of each HIV-1 competition. Furthermore, phylogenetic analyses based on a fitness matrix suggest that ex vivo fitness maps to the env and not the gag or pol genes. Discussion: Subtype C isolates are less fit than other subtypes but predominates in the HIV epidemic suggesting increased in vivo fitness. This dichotomy may be due to slower disease progression in subtype C-infected individuals resulting in an increased transmission time. In addition, subtype C may still be efficient at infecting LC, or cells thought to be the primary target for heterosexual transmission.

Keywords: AEGIS, HIV-1, Acquired Immunodeficiency Syndrome, HIV Infections, HIV Seropositivity, Disease Outbreaks, Genes, pol, Virus Replication, Prevalence, HIV-1 Reverse Transcriptase, Heterosexuality, Human, genetics, virology

020707
ThOrA1384