Correspondence

Correlation of Nonspecific Antiviral Activity with the Ability to Isolate Infectious Hiv-1 from Saliva

N Engl J Med 1994; 330:1314-1315May 5, 1994

Article

To the Editor:

Despite evidence of HIV in the saliva of HIV-positive persons, oral transmission of the virus appears to be a rare event. Researchers have isolated infectious virus from only a small percentage of saliva samples from HIV-infected patients, even when virus can be isolated from peripheral-blood samples from the same persons1,2 or when HIV DNA is detected in saliva by the polymerase chain reaction3.

Components of saliva can inhibit HIV4 and other viruses5. Can the presence of salivary viral inhibitors explain the low rate of recovery of HIV from oral fluids? Recently, we tested saliva samples from 21 HIV-positive persons to see whether they inhibited the replication of two RNA viruses (Sindbis and Newcastle disease) and one DNA virus (herpes simplex type 1). In the only sample from which infectious HIV was isolated, inhibitor levels for all three viruses tested were at or below the limits of detection, suggesting a correlation between the presence of infectious HIV in saliva and deficient levels of nonspecific viral inhibitors2.

To test the validity of this correlation, we conducted a blind test of inhibitor levels in 16 saliva samples previously used to determine the frequency of HIV isolation from saliva1. Two positive and 14 negative samples were coded and shipped to our laboratories in Texas for the determination of inhibitor titers. The antiviral titers (Table 1Table 1Correlation of Viral Inhibitor Levels in Saliva with the Isolation of Infectious HIV from Saliva.) of the saliva samples were determined with Sindbis and herpes simplex type 1 viruses2,5. The two samples from which virus had been isolated previously had undetectable levels of antiviral activity in these tests; all the other samples had appreciable antiviral activity. This inhibitory activity cannot be due to salivary antibodies, since there are essentially no antibodies to Sindbis viruses in the North American population. This correlation was statistically significant (P = 0.008 by two-tailed Fisher's exact test). There was no correlation between the isolation of HIV from saliva and the patients' CD4+ count or antiviral-medication status.

Testing for levels of viral inhibition in saliva with surrogate viral systems has the advantages of speed, sample conservation, and elimination of complications resulting from the presence of anti-HIV antibodies in saliva. The relation between antiviral activity and the salivary inhibition of HIV needs to be defined. This report confirms the existence of a correlation of low levels of nonspecific antiviral activity in saliva with the isolation of infectious HIV from saliva and suggests that the presence of salivary viral inhibitors is responsible for the observed low frequency of HIV in the oral cavity.

Dorian H. Coppenhaver, Ph.D.
Pat Sriyuktasuth-Woo, M.A.
Samuel Baron, M.D.
University of Texas Medical Branch, Galveston, TX 77555

Charles E. Barr, D.D.S.
M. Nasar Qureshi, M.D., Ph.D.
Beth Israel Medical Center, New York, NY 10003

5 References

1. 1

   Barr CE, Miller LK, Lopez MR, et al. Recovery of infectious HIV-1 from whole saliva. J Am Dent Assoc 1992;123:36-48
   Medline

2. 2

   Moore BE, Flaitz CM, Coppenhaver DH, et al. HIV recovery from saliva before and after dental treatment: inhibitors may have critical role in viral inactivation. J Am Dent Assoc 1993;124:67-74
   Web of Science | Medline

3. 3

   Yeung SC, Kazazi F, Randle CG, et al. Patients infected with human immunodeficiency virus type 1 have low levels of virus in saliva even in the presence of periodontal disease. J Infect Dis 1993;167:803-809
   CrossRef | Web of Science | Medline

4. 4

   Fultz PN. Components of saliva inactivate human immunodeficiency virus. Lancet 1986;2:1215-1215
   CrossRef | Web of Science | Medline

5. 5

   Coppenhaver DH, Baron JL, McKerlie ML, Sabados J, Baron S. Size and stability of a naturally occurring virus inhibitor. Antimicrob Agents Chemother 1984;25:646-649
   Web of Science | Medline

Citing Articles (11)

Citing Articles

1. 1

   Jonas Hardestam, Lisa Petterson, Clas Ahlm, Magnus Evander, Åke Lundkvist, Jonas Klingström. (2008) Antiviral effect of human saliva against hantavirus. Journal of Medical Virology 80:12, 2122-2126
   CrossRef

2. 2

   J Campo, MA Perea, J del Romero, J Cano, V Hernando, A Bascones. (2006) Oral transmission of HIV, reality or fiction? An update. Oral Diseases 12:3, 219-228
   CrossRef

3. 3

   Ana Ceballos, Guadalupe Andreani, Silvia E. Gonzalez Ayala, Yamila Romer, Isabel Rimoldi, María Rosa Agosti, Liliana Martinez Peralta. (2004) Epidemiological and Molecular Evidence of Two Events of Father-to-Child HIV Type 1 Horizontal Transmission. AIDS Research and Human Retroviruses 20:8, 789-793
   CrossRef

4. 4

   Zhiwei Wu, Ellis Golub, William R. Abrams, Daniel Malamud. (2004) gp340 (SAG) Binds to the V3 Sequence of gp120 Important for Chemokine Receptor Interaction. AIDS Research and Human Retroviruses 20:6, 600-607
   CrossRef

5. 5

   Miguel E Qui??ones-Mateu, Michael M Lederman, Zhimin Feng, Bikram Chakraborty, Jan Weber, Hector R Rangel, Michael L Marotta, Muneer Mirza, Bin Jiang, Patti Kiser, Kathy Medvik, Scott F Sieg, Aaron Weinberg. (2003) Human epithelial ??-defensins 2 and 3 inhibit HIV-1 replication. AIDS 17:16, F39-F48
   CrossRef

6. 6

   Zhiwei Wu, Donald Van Ryk, Cheryl Davis, William R. Abrams, Irwin Chaiken, John Magnani, Daniel Malamud. (2003) Salivary Agglutinin Inhibits HIV Type 1 Infectivity through Interaction with Viral Glycoprotein 120. AIDS Research and Human Retroviruses 19:3, 201-209
   CrossRef

7. 7

   MR Robinovitch, RL Ashley, JM Iversen, EM Vigoren, FG Oppenheim, M Lamkin. (2001) Parotid salivary basic proline-rich proteins inhibit HIV-1 infectivity. Oral Diseases 7:2, 86-93
   CrossRef

8. 8

   Samuel Baron, Indra Singh, Ashok Chopra, Dorian Coppenhaver, Jingzhi Pan. (2000) Innate antiviral defenses in body fluids and tissues. Antiviral Research 48:2, 71-89
   CrossRef

9. 9

   C. Scully, S. Porter. (2000) HIV topic update: oro-genital transmission of HIV. Oral Diseases 6:2, 92-98
   CrossRef

10. 10

    M. Nasar Qureshi, Charles E. Barr, Jason Reidy. (1996) Infection of oral mucosal cells by HIV-1. Perspectives in Drug Discovery and Design 5:1, 51-60
    CrossRef

11. 11

    CE Barr, MN Qureshi, Z Qiu, J Kaim, W Zhang. (1996) Oral HIV-1 recovery in the presence of periodontal disease. Oral Diseases 2:3, 198-201
    CrossRef