In regions of the world like West-Central Africa where multiple HIV-1 groups and subtypes co-circulate, the rate of dual infection - the concomitant or sequential infection with two or more genetically distinct HIV-1 strains is frequent, and recombinant viruses are common. A key characteristic of HIV-1 is its ability to recombine following dual infection, providing the virus with the opportunity for major evolutionary leaps and creating major challenges for diagnosis, treatment, vaccine design, and vaccine trials. Despite the fact that dual infection is common, information on how dual infection impacts on the host's anti-viral humoral immune responses is limited. Studying the impact of dual infection by discordant HIV-1 strains should increase our knowledge of the humoral immune response to diverse viruses. Therefore, the occurrence of dual infection provides a unique opportunity to investigate immune responses to multiple viral antigens and to study whether the host immune response is broadened when challenged with multiple, diverse antigens representing distinct viral subtypes and recombinant viruses. In the West-Central African country of Cameroon, multiple HIV-1 subtypes co-circulate, dual infection is common, and we have identified several individuals dually infected with diverse viruses who have remained asymptomatic and drug-naive for over 3-4 years. The occurrence of dual infections in these drug-naive individuals provides an opportunity to study virus evolution, to examine and compare the effect of infection by single and multiple subtypes on the host immune system in generating neutralizing antibodies, and to study whether such antibodies exhibit differences in their potency and breadth to autologous and/or heterologous viruses. These kinds of studies will shed light on the emergence of new viral subtypes and recombinants and contribute to the design of vaccines that will induce the most potent and broadly neutralizing antibodies to protect against diverse HIV-1 subtypes. Overall, these studies should improve our understanding of the relationship between HV-1 infection, protection, and immunity;and specifically, how HIV evades the immune system and how antiviral immunity impacts viral evolution. We therefore propose studies in:
AIM 1 : To examine the potency and breadth of neutralization against autologous and heterologous HIV-1 viruses by sequential plasma specimens from either individuals infected with single HIV-1 strains or dually infected with inter- or intra-subtype strains;
AIM 2 : To study the genetic evolution and emergence of recombinant viruses in the blood of dually (inter-subtype) infected subjects whose serum neutralizing antibodies display different patterns of breadth and potency;
and AIM 3 : To study the neutralization sensitivity of the recombinant viruses isolated from individuals with inter-subtype dual infections.

Public Health Relevance

The work proposed will study the impact on the humoral immune response and evolution of viruses in HIV-1 dually infected drug naive patients. The study will examine the potency and breadth of neutralizing antibodies in plasma of dually infected patients to autologous and heterologous viruses;and examine the emerging recombinant viruses in these patients and their susceptibility to neutralization. These studies should improve our knowledge on HIV-1 vaccine design and our understanding of the relationship between HV-1 infection, protection, and immunity;and specifically, how HIV evades the immune system and how antiviral immunity impacts viral evolution.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
AIDS Immunology and Pathogenesis Study Section (AIP)
Program Officer
Sanders, Brigitte E
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
New York University
Schools of Medicine
New York
United States
Zip Code
Courtney, Colleen R; Mayr, Luzia; Nanfack, Aubin J et al. (2017) Contrasting antibody responses to intrasubtype superinfection with CRF02_AG. PLoS One 12:e0173705
Nanfack, Aubin J; Redd, Andrew D; Bimela, Jude S et al. (2017) Multimethod Longitudinal HIV Drug Resistance Analysis in Antiretroviral-Therapy-Naive Patients. J Clin Microbiol 55:2785-2800
Courtney, Colleen R; Agyingi, Lucy; Fokou, Arlette et al. (2016) Monitoring HIV-1 Group M Subtypes in Yaoundé, Cameroon Reveals Broad Genetic Diversity and a Novel CRF02_AG/F2 Infection. AIDS Res Hum Retroviruses 32:381-5
Noubiap, Jean Jacques N; Aka, Peter V; Nanfack, Aubin J et al. (2015) Hepatitis B and C Co-Infections in Some HIV-Positive Populations in Cameroon, West Central Africa: Analysis of Samples Collected Over More Than a Decade. PLoS One 10:e0137375
Nanfack, Aubin J; Agyingi, Lucy; Noubiap, Jean Jacques N et al. (2015) Use of amplification refractory mutation system PCR assay as a simple and effective tool to detect HIV-1 drug resistance mutations. J Clin Microbiol 53:1662-71
Agyingi, Lucy; Mayr, Luzia M; Kinge, Thompson et al. (2014) The evolution of HIV-1 group M genetic variability in Southern Cameroon is characterized by several emerging recombinant forms of CRF02_AG and viruses with drug resistance mutations. J Med Virol 86:385-93
Courtney, Colleen; Mayr, Luzia; Nogueira, Lilian et al. (2014) Investigating Broad Neutralization in HIV-1 Non-B Subtype Infection in Yaounde, Cameroon. AIDS Res Hum Retroviruses 30 Suppl 1:A152
Duerr, Ralf; Soni, Sonal; Courtney, Colleen et al. (2014) Superinfected Patient Pseudovirus Exhibits Resistance to Broadly Neutralizing Antibodies, but Sensitivity to Autologous Plasma Post-superinfection. AIDS Res Hum Retroviruses 30 Suppl 1:A211
Andrabi, Raiees; Williams, Constance; Wang, Xiao-Hong et al. (2013) Cross-neutralizing activity of human anti-V3 monoclonal antibodies derived from non-B clade HIV-1 infected individuals. Virology 439:81-8
Mayr, Luzia M; Powell, Rebecca L; Ngai, Johnson N et al. (2012) Superinfection by discordant subtypes of HIV-1 does not enhance the neutralizing antibody response against autologous virus. PLoS One 7:e38989

Showing the most recent 10 out of 13 publications