European Journal of Clinical Investigation ( 1992) 22, 670-675

Antibody mediated enhancement of HIV-1 infection of an EBV transformed B cell line is CD4 dependent H. S . L. M. NOTTET, I. JANSE, N. M. DE VOS, L. J . BAKKER, M. R. VISSER & J. VERHOEF EijkmanWinkler Laboratory for Medical Microbiology, University of Utrecht, Utrecht, The Netherlands Received 21 January 1992 and in revised form 15 May 1992; accepted 28 May 1992

Abstract. Low levels of anti-viral antibodies may facilitate virus infection of Fc-receptor bearing cells. For human immunodeficiency virus (HIV) it has been reported that antibodies can enhance infection of phagocytic cells. We show that HIV-I can infect an Epstein-Barr virus transformed B cell line and that low levels of anti-HIV antibodies enhance infection. The enhanced infection was characterized by an increase in viral DNA and increased HIV p24 protein production. Detection of cell surface antigen expression of CD4, the receptor for HIV, Fc-receptor type I1 for IgG, but not of type I and I11 could be demonstrated by immunofluorescence cytometry. The enhancement was abrogated when infection was performed in presence of a monoclonal antibody directed against CD4. Based on these results we conclude that antibody mediated enhancement of HIV-I infection can also occur in non-phagocytic cells in a CD4 dependent manner and that IgG Fc-receptors other than types I or 111 are involved in this process. Keywords. Antibody mediated enhancement, B cell, CD4, EBV, HIV, IgG Fc-receptor. Introduction The humoral response of the host to viral infection directs the formation of a heterogenous population of specific antibodies. These antiviral antibodies can directly inhibit viral infection and indirectly in cooperation with other components of the host defense system such as complement and phagocytes. Some antibodies however fail to neutralize the virus and may even facilitate the viral infection. This phenomenon, called antibody mediated enhancement of viral infection (AME) has been described for a number of viruses [I]. It explains for example why Dengue virus is more dangerous for individuals with low levels of antidengue antibodies than in seronegative individuals [2]. AME has also been reported for human immunodeficiency virus type 1 (HIV-I) to occur in vitro in a monoblastoid cell line [3-81 and in cultured blood

mononuclear cells [9,10]. Antibodies that enhance HIV infectivity have been found in serum of infected individuals and infected and immunized animals [ I l,l2,13]. It has been suggested that the presence of these antibodies could explain the lack of protection of neutralizing or cytotoxic antibodies against HIV infection [14,15]. For the development of an HIV vaccine enhancing antibodies could be of a particular concern because an immunogen that would elicit their formation could pose serious risks to the immunized population. Enhancement of viral infectivity can also be mediated by complement [I]. Complement mediated enhancement (CME) of HIV-I infection has been described for a monoblastoid cell line [ 161, a T cell line [l7,18] and an Epstein-Barr virus (EBV) transformed B cell line [ 191. Some investigators demonstrated that in the presence of anti-HIV antibodies the C M E of HIV-I infection was augmented [ 19-25]. Depending on the cell type, requirement of complement receptor type 2 [I 8,19,22,25] and type 3 [ 161 has been reported. Antibody mediated enhanced HIV-I infection of a monoblastoid cell line is mediated by Fc-receptor type I for immunoglobulin G (FcyRI), but not by type I1 [5,8]. Homsy et al. [9] reported that only FcyRIII, and not FcyRI and FcyRII, was involved in the AME of HIV- 1. infection of monocyte-derived macrophages (MDM). They also showed AME of HIV-I infection of CD4+ lymphocytes but could not identify which type of Fc-receptor was involved [9]. For both cell types they reported that AME of HIV infection was CD4 independent [9], but others demonstrated that AME of HIV-I infection for MDM [lo] and a monoblastoid cell line [5-81 was CD4 dependent. Recently it has been reported that FcyRII mediates AME of dengue virus [26]. We studied the phenomenon of AME of HIV-1 infection of an EBV transformed B cell line. B cells d o not express FcyRl or FcyRIII, but d o express FcyRII [27]. Materials and methods Cells and virus

Correspondence: Hans S. L. M. Nottet, Eijkman-Winkler Laboratory for Medical Microbiology, University of Utrecht, AZU, hp (304.614. Heidelberglaan 100. 3584 CX Utrecht, The Netherlands.

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The EBV transformed B cell line NL+31 was kindly provided by D r T. Logtenberg, Department of Clinical

ANTIBODIES ENHANCE HIV INFECTION O F B CELLS Immunology, University of Utrecht. This cell line and the lymphoid cell lines H9H1V-’111h and SUP-TI were grown in RPMI1640 medium supplemented with 5 mM Hepes, 19 mM sodium bicarbonate, 10 pg ml-’ gentamicin and 10% heat-inactivated fetal bovine serum at 37°C in a 5% coz incubator. HIV-lIl[h was propagated in H9 cells and grown to high titer in SUPTI cells. TCIDso was determined with endpoint titration on SUP-TI cells and found to be lo7 ml-’. Antibodies Antibodies OKT4a (mouse IgG2a) and OKB7 (isotype control) were obtained from Ortho Diagnostics, Inc., Raritan, NJ, USA. Both antibodies were dialysed against phosphate buffered saline (PBS) to remove sodium azide. Anti-Leu3a (CD4), anti-Leu4 (CD3) and anti-Leu1 1 b (CD16) were obtained from Becton Dickinson and Co., Mountain View, CA, USA. Monoclonal antibody 197 was obtained from Medarex, W. Lebanon, NH. and KB61 was kindly provided by Dr Mason, Nuffield Department of Pathology, JRH, Oxford, UK. Heat inactivated (30 rnin at 56‘C) serum of an AIDS patient (CDC IV) was used as source for anti-HIV antibodies. Imm unojuorescen ce cy t onie t ry

In a volume of 20 pl lo6 cells were incubated with saturating concentrations of unconjugated monoclonal antibodies for 30 rnin at 4°C. Cells were washed twice with culture medium and incubated for 30 rnin at 4°C with F(ab’)z fluorescein isothiocyanate-conjugated goat anti mouse IgG (Tago Laboratories, Burlingame, CA, USA). Cells were washed three times with PBS, fixed in 2% paraformaldehyde and analyzed on a FACstar cytometer (Beckton Dickinson and Co., Mountain View, CA, USA). HIV-I titrution on N L + 3 1 cells Cells ( lo5 per well) were brought into 96 wells plates (Nunc, Denmark) and exposed to various dilutions of HIV-I in a total volume of 100 pl for 1 h. The cells were washed twice and brought into culture with 150 pl medium. One, 3, and 6 days after infection 50 pl supernatant was collected and stored at - 20°C for p24 antigen detection (Abbott Laboratories, North Chicago, IL, USA). On day 3 the cells were resuspended after the supernatant had been removed and 50 pl cell suspension was used for PCR analysis.

HIV-I infection of N L + 3 1 cells in the presence of diluted antiserum Virus and various antiserum dilutions were incubated for 10 rnin in a volume of 50 pl in a 96 wells plate (Nunc, Denmark). Then 50 pl cell suspension (lo5 cells) was added. Controls contained virus but no antiserum or contained neither virus nor antiserum. In

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HIV- 1 infection blocking experiments the cells were preincubated with 5 pg ml-’ OKT4A or OKB7 monoclonal antibodies for 15 min at 4°C. After infection for 1 h unbound virus was removed by washing with culture medium and the cells were cultured in 150 pl medium. On days 2 and 5 respectively, 75 and 100 pl medium was replaced. On day 6 50 pI supernatant was collected and stored at - 20°C for p24 antigen detection. The cells were suspended and 50 pl was used for PCR analysis. The remaining cells were used for propagation of the culture. Three times a week part of the culture medium was replaced and with regular intervals 50 pl supernatant was collected and stored at - 20°C for p24 antigen detection.

PCR unalysis Cells were washed with PBS and lysed in PCR lysis buffer (10 mM Tris hydrochloride [pH 8.31, 1 mM EDTA, 0.5% Triton x 100, O~OOI‘l/a sodium dodecyl sulfate) with 300 pg ml-’ proteinase K (Merck, Darmstadt, Germany). The lysed cells were digested with proteinase K for 1 h at 55°C followed by enzyme inactivation for 10 rnin at 94°C. The lysates were stored at -20°C until they were used. Crude cell extracts corresponding to lo4 cells were used for amplification (94°C for 1 min, 55°C for I min, 72°C for 1 rnin.) for the [)-globin gene and the ENV region of HIV-I in an automated thermal cycler (Perkin Elmer Cetus) using 10 p ml-’ Taq polymerase (Perkin Elmer Cetus). First amplification step was performed with HIV primers A (sense 5’ACCTGGAGGAGGAGATATGA3’) and B (antisense 5’CCCTGCCTAACTCTATTCAC3’) and /?-globin primers E (sense S’GGTTGGCCAATCTACTCCCAGG3’) and F (antisense S’GCTCACTCAGTGTGGCAAAG3’1 for 25 cycles. Second amplification steps were performed on a thousand fold dilution of the first reaction. Amplification with primers C (sense S’CAATTTGCTGAGGGCTATTG3’) and D (antisense S’CCAAGCCTCCTACTATCATT3’) was performed for 25 cycles, yielding a 419 bp HIV-1 fragment. Amplification for 15 cycles with primers G (sense S’GTCAGGGCAGAGCCATCTATT3’) and primer H (antisense S’CTTGATACCAACCTGCCCAG3’) resulted in a 175 bp /?globin fragment. The products of the second PCR were analysed by electrophoresis on a 2% agarose gel stained with ethidium bromide. Results

Because in previous studies enhancement of infection has been reported to occur only at low multiplicity of infection (MOI), the lowest virus load at which infection could be detected was determined and was regarded as the optimal dose to detect AME. Therefore HIV-llllh was titrated on the NL + 3 I cells. After 3 days cells were collected for PCR analysis and on days I , 3 and 6 supernatant was collected for p24 antigen detection. From Fig. 1 it appears that at least lo3

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HIV ENV 0 - g lobi n

1 2 3 4 5 6 7 8 9 1 0 Figure 1. HIV-llllb titration on N L + 3 I cell as determined by PCR analysis. The presence of viral DNA was analysed 3 days after infection with MOI of 1 (lane I ), of 0. I (lane 2). of0.01 (lane 3), of0.001 (lane 4). 0.0001 (lane 5 ) and 0 (lane 6 ) .Controls are no cells (lane 7). U9vH" with only 8-globin primers (lane 8) and with only HIV ENV primers (lane 9). Marker (lane 10) is lambda phage DNA digested with Pstl. The sizes of the HIV ENV and 8-globin fragments are 419 bp and 175 bp respectivcly.

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lo-'") did not result in detectable virus infection. Enhancement of HIV-I infection was detected at very high serum dilutions as determined by PCR (Fig. 3 ) and p24 production (Fig. 4) and varied between serum dilution l o p 6and lo-'. The presence of viral DNA in these cells preceded the p24 antigen release into the supernatant. Evaluation of AME of HIV-I infection by p24 antigen production showed that the degree of enhancement varied among the experiments and was on averagefold four times higher than the infection without serum. Cells infected in presence of the serum dilution which causes enhancement remained the highest p24 producing cells throughout the culture period (Fig. 4). In experiments where heat-inactivated human pooled serum of HIV-I seronegative donors to IO-"'no effect on HIV-I was used at dilutions infectivity was observed. T o investigate whether the enhanced HIV- I infection is CD4 dependent or is solely a Fc-receptor mediated process surface antigen expression on the NL+31 cells was studied. As expected [27,28] immunofluorescence cytometry revealed that Fcy RII was expressed while expression of type I and 111 Fcreceptor was absent on these cells (Fig. 5 ) . Moderate levels of CD4 molecules were also present on the surface of the cells. To further explore the nature of the enhanced infection mediated by anti-HIV antibodies blocking experiments with the monoclonal antibody OKT4A (against CD4) and the isotype control OKB7 were performed. In all experiments AME was detected and was blocked by OKT4A (Fig. 6). Cells which were

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days after infection

Figure 2. HIV-llllb titration on NL+31 cells as determined by p24 antigen production.

virions per lo5cells (MOI 0.01) were required to detect viral DNA, 3 days after infection using PCR-techniques. Determination of the p24 antigen production revealed that 1 O3 or even 10' virions per 1Os cells (MOI 0.01 or 0.001) caused productive infection 6 days after infection (Fig. 2). To investigate if the presence of anti-HIV antibodies can cause enhancement of HIV- I infection of NL + 3 I cells an MOI of 0.001 was used for the AME studies. The source of anti-HIV antibodies was a heat-inactivated (30 min, 56°C) human serum which exhibited no neutralising activity at a dilution of 1/100. Incubation of NL+31 cells with various serum dilutions ( l o - ' to

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Figure 3. Antibody mediated enhancement of HIV-llllb infection of NL+31 cells as determined by PCR analysis. Cells were analysed for the presence of viral DNA 6 days after infection with a MOI of0.001. Cells were infected in presence of the antiserum dilutions 10 4(lane I ) , 10 '(lane2), 10 '(lane3). 10 '(lane4). IO-*(laneS), 10-9(lane6), 10 I0(lane7),and 10 'l(lane8),no antiserum (lane 9) or not infected (lane 10). Controls are no cells (lane I I). U 9 3 ~ ~with ' " only b-globin primers (lane 12) and with only HIV ENV primers (lane 13). Marker (lane 14) is lambda phage DNA digested with Hind111 and EcoR I . The sizes of the HIV ENV and 8-globin fragments are 419 bp and 175 bp respectively.

p24 (nglrnl)

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[29,30,3I]. Because most EBV+ B cells produced higher amounts of HIV-I than their EBV- counterparts [30] we considered an EBV+ B cell as a good model for studying the AME of HIV-I infection of a non-phagocytic cell. We tested several EBV transformed B cell lines (including NL 3 1) for susceptibility to HIV-I infection and found that all of them could be infected (data not shown). The cell line NL+31 produced the highest amount of p24 after HIV-I infection. Theoretically, antibodies can mediate HIV infection by three mechanisms: 1) phagocytosis of opsonised virus whereby fusion of the virusmembrane with the endosome occurs before phagosome-lysosome fusion; 2) fusion between viral and cellular membrane after binding to the FcyR; 3) CD4 mediated infection by increasing CD4-virus interaction through FcyR. In our model the first mechanism is excluded. The second mechanism, whereby the FcyR serves as an alternative HIV receptor, is not supported by our results because AME was found to be CD4 dependent. Several other investigators also reported that the nature of AME of HIV- 1 infection [5-8,101 is CD4 dependent. Therefore it seems likely that antibodies promote virus-CD4 binding and subsequently infection by increasing virus cell contact through FcyR. However, FcyRIII [9] and a cytomegalovirus induced FcyR [32] have been described as alternative HIV-I infection routes. B cells (like NL+31) d o not express FcyRI or FcyRIII, but do express FcyRII. FcyRII is a complex genetic locus encoded by a minimum of three genes from which the IIB gene is expressed on B cells [28].

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serum dilution (in 10 log) Figure 4. Kinetics of antibody mediated enhanced HIV-llllh infection of NL+31 cells as determined by p24 antigen production.

pretreated with OKB7 showed no inhibition of AME compared to cells which were pretreated with PBS.

Discussion The results of this study demonstrate that EBV transformed B cells are susceptible to HIV-I infection and that this infection is enhanced by low levels of serum obtained from a patient with acquired immunodeficiency syndrome. Furthermore, it is demonstrated that the (enhancement oQ infection is CD4 dependent. Receptivity of EBV-genome positive B cells to infection with HIV-I has been described by others

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fluorescence intensity Figure 5. Expression of CD4 and FcyRIl on NLc 3 I cells as determined by immunofluorescence cytometry. Cells were incubated with control monoclonal antibody anti-Leu4 (dotted lines) and (A) the C D 4 specific anti-Leu3a (uninterrupted line), (B) the FcyRI specific MoAb 197 (uninterrupted line), (C) the FcyRIl specific MoAb KB61 (uninterrupted line) and (D) the FcyRIII specific MoAb anti-Leu1 Ib (uninterrupted line).

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Figure 6. Antibody mediated enhancement of HIV-I infection of N L + 3 1 cells is CD4 dependent as determined by p24 antigen production.

Several monoclonal antibodies have been raised against FcyRII but none have the potential to block binding to the FcyRIIB molecule. Nevertheless we performed blocking studies with MoAb KB61 [33] but were not able to reduce the enhanced infection (data not shown). Although the involvement of FcyRIIB is not certain a role for FcyRI and FcyRIII is excluded. The involvement of FcyRI in the AME of HIV

infection is reported by Matsuda et ul. and Takeda et al. [5,8] while Homsy et ul. [9] reported the FcyRIlI mediated viral entry. It has been reported that complement mediates enhancement of HIV infection of EBV transformed B cells in absence [I91 and in presence of antibodies [ 19,251. In contrast to our results Tremblay et al. could not detect AME of HIV infection of EBV+ B cells [25]. In that study however serum dilutions of lo-' and l o p 4 were used for the experiments while we detected AME at higher serum dilutions (lo-' to lo-'). Whereas for flaviviruses such as dengue virus antibodies enhance infectivity up to 1000-fold [l], the AME of HIV infectivity is modest. In a recent study, Shadduck et al. [34] described the lack of enhancing activity of 14 HIV antibody-positive sera. Therefore it is difficult to speculate about the in uiuo relevance of AME of HIV infection. Homsey et al. [35] describe a correlation between serum enhancement and disease progression. Using sequential pairs of HIV and sera they found that the enhancing activity of some sera increased over time and suggested that enhancing antibodies contribute to the spread and pathogenesis of HIV. Although we detected enhancement under stringent conditions (low MOI and very low serum concentrations) these conditions may exist during the early course of infection and as a result of antigenic drift also for new HIV variants during the progress of the disease.

ANTIBODIES ENHANCE HIV INFECTION OF B CELLS References 1 Porterfield JS. Antibody-dependent enhancement ofviral infectivity. Adv Vir Res 1986;31:335-55. 2 Halstead SB. Pathogenesis of dengue: challenges to molecular

biology. Science 1988;239:476 8 I . 3 Takeda A. Tuazon CU. Ennis FA. Antibody-enhanced infection by HIV- I via Fc receptor-mediated entry. Science 1988;242:5803. 4 Jouault T. Chapuis F, Olivier R. Parravicini C, Bahraoui E. Gluckman JC. HIV infection of monocytic cells: rble of antibody-mediated virus binding to Fc-gamma receptors. AIDS 1989;3:125-33. 5 Matsuda S, Gidlund M, Chiodi F. Cafaro A, Nygren A. Morein B, Nilsson K. Feny6 EM, Wigzell H. Enhancement of human immunodeficiency virus (HIV) replication in human monocytes by low titres of anti-HIV antibodies in t:irro. Scand J Immunol 1989:30:425 34. 6 Zeira M, Byrn RA,Groopman JE. Inhibitionofserum-enhanced HIV-I infection of U937 monocytoid cells by recombinant soluble CD4 and antLCD4 monoclonal antibody. AIDS Res Human Retroviruses 1990;6:629-39. 7 Takeda A, Ennis FA. FcR-mediated enhancement of HIV-I infection by antibody, AIDS Res Human Retroviruses 3990;6:999~1005. 8 Takeda A. Sweet RW, Ennis FA. Two receptors are required for antibody-dependent enhancement of human immunodeficiency virus type 1 infection: CD4 and FcyR. J Virol 1990;64:5605 10. 9 Honisy J, Meyer M, Tateno M, Clarkson S. Levy JA. The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells. Science I989;244:1357- 60. 10 Perno CF. Baseler MW. Broder S. Yarchoan R. Infection of monocytes by human immunodeficiency virus type 1 blocked by inhibitors of CD4-gp120 binding, even in the presence of enhancing antibodies. J Exp Med 1990;171:1043-56. I 1 Homsy J, Tateno M, Levy JA. Antibody-dependent enhancement of HIV infection. Lancet 1988;i:1285 6 . 12 Montefiori DC, Robinson WE jr, Hirsch VM. Modliszewski A , Mitchell WM, Johnson PR. Antibody-dependent enhancement of simian immunodeficiency virus (SIV) infection in vi/ro by plasma from SIV-infected rhesus macaques. J Virol 1990;64:113 9. 13 Montefiori DC. Murphy-Corb M. Desrosiers RC, Daniel MD. Complement-mediated, infection-enhancing antibodies in plasma from vaccinated macaques before and after inoculation with live simian immunodeficiency virus. J Virol 1990;64:5223 5. 14 Robinson WE jr, Monteliori DC. Mitchell WM. Will antibodydependent enhancement of HIV-I infection be a problem with AIDS vaccines'? Lancet 19X8;i:830-1. 15 Barnes DM. Another glitch for AIDS vaccines? Science 1988;241:533 4. I6 Reisinger EC, Vogetseder W. Berzow D. K6fler D. Bitterlich G. Lehr HA, Wachter H, Dierich MP. Complement-mediated enhancement of HIV-I infection of the monoblastoid cell line U937. AIDS 1990;4:961-5. 17 Montefiori DC. Robinson WE jr. Mitchell WM. Antibodyindependent. complement-mediated enhancemcnt of HIV-I infection by inannosidase I and 11 inhibitors. Antiviral Res 1989;l 1:137 46. 18 Boyer V. Desgranges C. Trabaud MA, Fischer E. Kazatchkine MD. Complement mediates human immunodeficiency virus type I infection of a human T cell line in a CD4- and antibodyindependent fashion. J Exp Med 1991;173:1151 8 . 19 Gras GS, Dormont D. Antibody-dependent and antibodyindependent complement-mcdiatcd enhancement of human

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immunodeficiency virus type 1 infectin in a human, Epstein-Barr virus-transformed B-lymphocytic cell line. J Virol 1991;65:5415. 20 Robinson WE jr, Montefiori DC, Mitchell WM. Antibodydependent enhancement of human immunodeficiency virus type 1 infection. Lancet 1988;i:790 4. 21 Robinson WE jr, Montefiori DC, Gillespie DH. Mitchell WM. Complement-mediated, antibody-dependent enhancement of HIV-I infection in zitro is characterized by increased protein and RNA syntheses and infectious virus release. J Acq Irnmun Def Synd 1989;2:33-42. 22 Robinson We jr, Montefiori DC. Mitchell WM. Complementmediated antibody-dependent enhancement of HIV-I infection requires C D 4 and complement receptors. Virology 1990;I75:600-4. 23 Robinson WE jr, Kawamura T, Gorny MK, Lake D. Xu JY, Matsumoto Y,Sugano T, Masuho Y . Mitchell W M , Hersh E, Zolla-Pazner S . Human monoclonal antibodies to the human immunodeficiency virus type I (HIV-I) transmembrane glycoprotein gp41 enhance HIV-I infection in r i m . Proc Nail Acad Sci USA 1990;87:3185-9. 24 Robinson W E jr, Kawamura T, Lake D. Masuho Y , Mitchell WM, Hersh EM. Antibodies to the primary immunodominant domain of human immunodeficiency virus type I (HIV-I) glycoprotein gp41 enhance HIV-I infection in iii/ro. J Virol 1990;64:5301~5. 25 Tremblay M, Meloche S, Sekaly RP, Wainberg MA. Complement receptor 2 mediates enhancement of human immunodeficiency virus I infection in Epstein-Barr virus-carrying B cells. J Exp Med 1990;171:1791 -6. 26 Littaua R, Kurdne 1, Ennis FA. Human IgG Fc receptor 11 mediates antibody-dependent enhancement of dengue virus infection. J Immunol 1990;144:3183-6. 27 Unkeless JC. Function and heterogeneity of human Fc receptors for immunoglobulin G. J Clin Invest 1989;83:355-61. 28 Ravetch JV. Kinet JP. Fc receptors. Annu Rev Immunol 1991;9:457-92 29 Salahuddin SZ. Ablashi DV, Hunter EA, Gonda MA, Sturzenegger S , Markham PD, Gallo RC. HTLV-111 infection of EBVgenome-positive B-lymphoid cells with or without detectable T4 antigens. Int J Cancer 1987:39: 198-202. 30 Monroe JE, Calender A, Mulder C. Epstein-Barr virus positive and -negative B-cell lines can be infected with human immunodeficiency virus types I and 2. J Virol 1988;62:3497-500. 31 Dahl KE. Burrage T, Jones F. Miller G. Persistent nonproductive infection of Epstein-Barr virus-transformed human B lymphocytes by human immunodeficiency virus type I . J Virol 1990;64:1771-83. 32 McKeating JA, Griffiths PD, Weiss RA. HIV susceptibility conferred to human fibroblasts by cytomegalovirus-induced Fc receptor. Nature 1990;343:659-61. 33 Pulford K, Ralfkiaer E. Macdonald SM, Erber WN, Falini B. Gatter KC, Mason DY. A new monoclonal antibody (KB61) recognizing a novel antigen which is selectively expressed on a subpopulation of human B lymphocytes. Immunology l986;57:7 1-6. 34 Shadduck PP, Weinberg JB. Haney AF. Bartlett JA, Langlois AJ, Bolognesi DP. Matthcws TJ. Lack of enhancing effect of human anti-human immunodeficiency virus type 1 (HIV-I) antibody on HIV-I infection of human blood monocytes and peritoneal macrophages. J Virol 1991;65:4309- 16. 35 Homsy J, Meyer M, Levy JA. Serum enhancement of human immunodeficiency virus (HIV) infection correlates with disease in HIV-infected individuals. J Virol 1990;64:1437 -40.

Antibody mediated enhancement of HIV-1 infection of an EBV transformed B cell line is CD4 dependent.

Low levels of anti-viral antibodies may facilitate virus infection of Fc-receptor bearing cells. For human immunodeficiency virus (HIV) it has been re...
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