Perinatal infection has provided a valuable model for studying HIV-1 evolution and disease progression. However, most studies on disease progression and viral evolution have focused on infected adults of developed countries infected by Clade B virus. Very little is known about disease progression associated with non-Clade B viruses, especially in children in developing countries with an HIV-1 epidemic. An example is Zambia, a sub-Saharan African nation located in the I-IIV-1 belt, with a very high incidence of HIV-1 infection. Our preliminary studies in women of childbearing age have shown an HIV-1 seroprevalence of about 35 percent. HIV-1 isolates from Zambia belong to the non-Clade B subgroups. In the absence of anti-retroviral therapy, many of the babies born to these mothers will be infected by HIV-I. The objective of the proposed work is to understand HIV-1 evolution in an epidemic region in the absence of selection pressure due to anti-retroviral therapy, so that strategies can be developed to block their replication and transmission. Our immediate goal is to longitudinally isolate and characterize Clade C viruses from infants infected by HIV-1 perinatally in Zambia. This proposal will make use of an ongoing study on the transmission of Kaposi's sarcoma :associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) from Zambia. Using the developed infrastructure at the University Teaching Hospital in Zambia, its ongoing recruitment of mother/infant pairs at delivery and at follow-ups, we will longitudinally collect non-Clade B local viral isolates for this project.
The specific aims are: 1) to isolate Zambian non-Clade B HIV-1 samples from infected infants longitudinally, and study their biological properties and host cell tropism; 2) to characterize patterns of genetic diversity and sequence evolution of longitudinal HIV-1 isolates from infected infants; 3) to integrate the virological and genetic analyses of longitudinal HIV-1 isolates with clinical disease manifestations. This study will generate important information about the evolution of Clade C strains in Zambia.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD039620-01A2
Application #
6450252
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Moye, Jack
Project Start
2001-09-26
Project End
2006-08-31
Budget Start
2001-09-26
Budget End
2002-08-31
Support Year
1
Fiscal Year
2001
Total Cost
$317,250
Indirect Cost
Name
University of Nebraska Lincoln
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
555456995
City
Lincoln
State
NE
Country
United States
Zip Code
68588
Siddappa, Nagadenahalli B; Song, Ruijiang; Kramer, Victor G et al. (2009) Neutralization-sensitive R5-tropic simian-human immunodeficiency virus SHIV-2873Nip, which carries env isolated from an infant with a recent HIV clade C infection. J Virol 83:1422-32
Kong, Xiaohong; West, John T; Zhang, Hong et al. (2008) The human immunodeficiency virus type 1 envelope confers higher rates of replicative fitness to perinatally transmitted viruses than to nontransmitted viruses. J Virol 82:11609-18
Hoffmann, Federico G; He, Xiang; West, John T et al. (2008) Genetic variation in mother-child acute seroconverter pairs from Zambia. AIDS 22:817-24
Zhang, Hong; Hoffmann, Federico; He, Jun et al. (2006) Characterization of HIV-1 subtype C envelope glycoproteins from perinatally infected children with different courses of disease. Retrovirology 3:73
Song, R J; Chenine, A-L; Rasmussen, R A et al. (2006) Molecularly cloned SHIV-1157ipd3N4: a highly replication- competent, mucosally transmissible R5 simian-human immunodeficiency virus encoding HIV clade C Env. J Virol 80:8729-38
Wood, Charles; Harrington Jr, William (2005) AIDS and associated malignancies. Cell Res 15:947-52
Wang, Jinzhong; Zhang, Jun; Zhang, Luwen et al. (2005) Modulation of human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus replication and transcription activator transactivation by interferon regulatory factor 7. J Virol 79:2420-31
Zhang, Hong; Hoffmann, Federico; He, Jun et al. (2005) Evolution of subtype C HIV-1 Env in a slowly progressing Zambian infant. Retrovirology 2:67
Grisson, Ricky D; Chenine, Agnes-Laurence; Yeh, Lan-Yu et al. (2004) Infectious molecular clone of a recently transmitted pediatric human immunodeficiency virus clade C isolate from Africa: evidence of intraclade recombination. J Virol 78:14066-9
Zhang, Hong; Orti, Guillermo; Du, Qiujiang et al. (2002) Phylogenetic and phenotypic analysis of HIV type 1 env gp120 in cases of subtype C mother-to-child transmission. AIDS Res Hum Retroviruses 18:1415-23